Trial Outcomes & Findings for A Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia (NCT NCT03583697)

NCT ID: NCT03583697

Last Updated: 2024-06-13

Results Overview

A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. A severity grade was defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. Safety Population includes all sentinel and randomized participants in the FAS who received at least one dose of vosoritide or placebo in this study. Serious adverse event (SAE)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 75 participants
• Primary outcome timeframe: Up to Week 56 (Safety Follow-Up +/-7d)
• Results posted on: 2024-06-13

Participant Flow

This was a multi-center study conducted by 16 principal investigators at 16 study centers in four countries (United States, Australia, United Kingdom and Japan).

A total of 75 participants (full analysis set [FAS]) were enrolled into the study, of which 11 participants were enrolled to receive vosoritide (sentinel participants). 64 participants were blinded and randomized to receive vosoritide or placebo (32 randomized for vosoritide and 32 for placebo), which constituted the FAS (randomized).

Participant milestones

Measure	Sentinel Cohort 1 Sentinel: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=4) Cohort 2 Sentinel: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/ kg/day single daily subcutaneous injection (n=4) Cohort 3 Sentinel: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=3)	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)
Overall Study STARTED	11	32	32
Overall Study Cohort 1: Age >= 24 to < 60 Months	4	15	16
Overall Study Cohort 2: Age >= 6 to < 24 Months	4	8	8
Overall Study Cohort 3: Age 0 to < 6 Months	3	9	8
Overall Study COMPLETED	11	31	31
Overall Study NOT COMPLETED	0	1	1

Reasons for withdrawal

Measure	Sentinel Cohort 1 Sentinel: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=4) Cohort 2 Sentinel: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/ kg/day single daily subcutaneous injection (n=4) Cohort 3 Sentinel: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=3)	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)
Overall Study Withdrawal by Subject	0	0	1
Overall Study AE of sudden infant death syndrome, not related	0	1	0

Baseline Characteristics

Full analysis population (FAS).

Baseline characteristics by cohort

Measure	Sentinel n=11 Participants Cohort 1 Sentinel: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=4) Cohort 2 Sentinel: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=4) Cohort 3 Sentinel: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=3)	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Total n=75 Participants Total of all reporting groups
Age, Continuous	24.71 Months STANDARD_DEVIATION 20.79 • n=11 Participants	24.39 Months STANDARD_DEVIATION 16.83 • n=32 Participants	27.82 Months STANDARD_DEVIATION 19.25 • n=32 Participants	25.90 Months STANDARD_DEVIATION 18.30 • n=75 Participants
Sex: Female, Male Female	3 Participants n=11 Participants	15 Participants n=32 Participants	19 Participants n=32 Participants	37 Participants n=75 Participants
Sex: Female, Male Male	8 Participants n=11 Participants	17 Participants n=32 Participants	13 Participants n=32 Participants	38 Participants n=75 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=11 Participants	3 Participants n=32 Participants	3 Participants n=32 Participants	6 Participants n=75 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=11 Participants	29 Participants n=32 Participants	29 Participants n=32 Participants	69 Participants n=75 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=11 Participants	0 Participants n=32 Participants	0 Participants n=32 Participants	0 Participants n=75 Participants
Race/Ethnicity, Customized White	8 Participants n=11 Participants • Full analysis population (FAS).	21 Participants n=32 Participants • Full analysis population (FAS).	25 Participants n=32 Participants • Full analysis population (FAS).	54 Participants n=75 Participants • Full analysis population (FAS).
Race/Ethnicity, Customized Asian-Other	1 Participants n=11 Participants • Full analysis population (FAS).	6 Participants n=32 Participants • Full analysis population (FAS).	2 Participants n=32 Participants • Full analysis population (FAS).	9 Participants n=75 Participants • Full analysis population (FAS).
Race/Ethnicity, Customized Asian-Japanese	0 Participants n=11 Participants • Full analysis population (FAS).	4 Participants n=32 Participants • Full analysis population (FAS).	4 Participants n=32 Participants • Full analysis population (FAS).	8 Participants n=75 Participants • Full analysis population (FAS).
Race/Ethnicity, Customized Multiple	2 Participants n=11 Participants • Full analysis population (FAS).	1 Participants n=32 Participants • Full analysis population (FAS).	0 Participants n=32 Participants • Full analysis population (FAS).	3 Participants n=75 Participants • Full analysis population (FAS).
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=11 Participants • Full analysis population (FAS).	0 Participants n=32 Participants • Full analysis population (FAS).	1 Participants n=32 Participants • Full analysis population (FAS).	1 Participants n=75 Participants • Full analysis population (FAS).
Weight	10.12 Kg STANDARD_DEVIATION 3.70 • n=11 Participants	10.20 Kg STANDARD_DEVIATION 3.83 • n=32 Participants	10.55 Kg STANDARD_DEVIATION 4.31 • n=32 Participants	10.34 Kg STANDARD_DEVIATION 3.98 • n=75 Participants
Weight Z-Score	-1.41 Z-Score STANDARD_DEVIATION 0.73 • n=11 Participants	-1.49 Z-Score STANDARD_DEVIATION 1.26 • n=32 Participants	-1.59 Z-Score STANDARD_DEVIATION 1.44 • n=32 Participants	-1.52 Z-Score STANDARD_DEVIATION 1.27 • n=75 Participants
BMI	20.06 kg/m^2 STANDARD_DEVIATION 1.87 • n=11 Participants	19.48 kg/m^2 STANDARD_DEVIATION 2.45 • n=32 Participants	20.14 kg/m^2 STANDARD_DEVIATION 2.39 • n=32 Participants	19.85 kg/m^2 STANDARD_DEVIATION 2.34 • n=75 Participants
BMI Z-Score	2.79 Z-Score STANDARD_DEVIATION 0.98 • n=4 Participants • BMI Z-Scores were derived only for participants aged 24 months or older. Hence, participants in Cohort 2 (n=Sentinel 4, Vosoritide 8, Placebo 8) and Cohort 3 (n=Sentinel 3, Vosoritide 9, Placebo 8) were are not included.	2.52 Z-Score STANDARD_DEVIATION 1.15 • n=15 Participants • BMI Z-Scores were derived only for participants aged 24 months or older. Hence, participants in Cohort 2 (n=Sentinel 4, Vosoritide 8, Placebo 8) and Cohort 3 (n=Sentinel 3, Vosoritide 9, Placebo 8) were are not included.	2.77 Z-Score STANDARD_DEVIATION 0.75 • n=16 Participants • BMI Z-Scores were derived only for participants aged 24 months or older. Hence, participants in Cohort 2 (n=Sentinel 4, Vosoritide 8, Placebo 8) and Cohort 3 (n=Sentinel 3, Vosoritide 9, Placebo 8) were are not included.	2.67 Z-Score STANDARD_DEVIATION 0.94 • n=35 Participants • BMI Z-Scores were derived only for participants aged 24 months or older. Hence, participants in Cohort 2 (n=Sentinel 4, Vosoritide 8, Placebo 8) and Cohort 3 (n=Sentinel 3, Vosoritide 9, Placebo 8) were are not included.

PRIMARY outcome

Timeframe: Up to Week 56 (Safety Follow-Up +/-7d)

Population: Safety Population: The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study.

A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. A severity grade was defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.

Safety Population includes all sentinel and randomized participants in the FAS who received at least one dose of vosoritide or placebo in this study.

Serious adverse event (SAE)

Outcome measures

Measure	Cohort 1: Placebo n=11 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) Participants with any AE	11 Participants	32 Participants	32 Participants	—	—	—
Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) Participants with any SAE	0 Participants	3 Participants	6 Participants	—	—	—
Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) Participants with any treatment-related AE	8 Participants	29 Participants	17 Participants	—	—	—
Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) Participants with any treatment-related SAEs	0 Participants	0 Participants	0 Participants	—	—	—
Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) Participants with any AE of CTCAE grade >=3	0 Participants	2 Participants	3 Participants	—	—	—
Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) Participants who died	0 Participants	1 Participants	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: FAS \& FAS (randomized) population:The FAS (randomized) was a subset of the FAS, which included 64 participants who were randomized to study treatment (32 participants randomized to vosoritide \& 32 participants randomized to placebo). This is model-based analysis, it is true that the participants analyzed for placebo FAS \& FAS (randomized) are the same, but participants analyzed for vosoritide arm FAS \& FAS(randomized) are different, that's why the model-based results for placebo are different

Z-Scores were derived using age-sex specific reference data (means and SDS) for average stature children per the Centers for Disease Control and Prevention. A height Z score of 0 would indicate that the subject's height is equal to the mean height for the average stature population of the same sex and age. A positive height Z score indicates that the subjects height is above the mean height for the average stature population of the same sex and age, whilst a negative height Z score indicates that the subjects height is below the mean height for the average stature population of the same sex and age. To conclude if the height Z score increases then this means the height deficit has decreased.

standard deviation score (SDS).

The primary efficacy analysis population was the subset of randomized participants in the FAS.

Outcome measures

Measure	Cohort 1: Placebo n=32 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=43 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=32 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Height Z-score at Week 52.	-0.06 Z-score Interval -0.26 to 0.15	-0.31 Z-score Interval -0.48 to -0.13	0.01 Z-score Interval -0.15 to 0.17	-0.30 Z-score Interval -0.47 to -0.13	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS (randomized) Population and FAS population. This is model-based analysis, it is true that the participants analyzed for placebo FAS \& FAS (randomized) are the same, but participants analyzed for vosoritide arm FAS \& FAS (randomized) are different, that's why the model-based results for placebo are different.

As a general rule, standing height/sitting height was used if participants were aged >= 24 months at baseline. Body length/crown to rump was used if participants were aged < 24 months at baseline. If body length was not measured and standing height was available, standing height was used.

Outcome measures

Measure	Cohort 1: Placebo n=32 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=43 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=32 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Height at Week 52	8.15 cm Interval 7.55 to 8.75	7.38 cm Interval 6.87 to 7.89	8.41 cm Interval 7.93 to 8.89	7.45 cm Interval 6.95 to 7.95	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS (randomized) Population and FAS population. This is model-based analysis, it is true that the participants analyzed for placebo FAS \& FAS (randomized) are the same, but participants analyzed for vosoritide arm FAS \& FAS (randomized) are different, that's why the model-based results for placebo are different.

AGV was derived over 12-month intervals starting from the baseline visit. Annualized growth velocity (AGV) = Standing Height at Date 2 - Standing Height at Date 1/Interval Length (Days) x 365.25.

Difference in LS means were obtained from an analysis of covariance model.

Outcome measures

Measure	Cohort 1: Placebo n=32 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=43 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=32 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Annualized Growth Velocity (AGV) at Week 52	-2.17 cm/year Interval -2.76 to -1.58	-2.95 cm/year Interval -3.45 to -2.45	-2.41 cm/year Interval -2.88 to -1.94	-3.32 cm/year Interval -3.81 to -2.84	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS (randomized) Population and FAS population. This is model-based analysis, it is true that the participants analyzed for placebo FAS \& FAS (randomized) are the same, but participants analyzed for vosoritide arm FAS \& FAS (randomized) are different, that's why the model-based results for placebo are different.

Upper to Lower Body ratio=Sitting Height / (Standing Height - Sitting Height).

Outcome measures

Measure	Cohort 1: Placebo n=32 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=43 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=32 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Upper to Lower Body Segment Ratio at Week 52	-0.20 Ratio Interval -0.28 to -0.13	-0.13 Ratio Interval -0.21 to -0.06	-0.19 Ratio Interval -0.25 to -0.13	-0.13 Ratio Interval -0.2 to -0.06	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population. Change from baseline was based on the participants with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available.

Change from baseline in other growth measures (upper body length, head circumference, arm span, upper arm length, lower arm (Forearm) length, Lower Body Length, Upper Leg Length (Thigh), knee to heel length, and tibial length) at Week 52.

Participants aged <24 months, body length and crown to rump length take precedence over standing height and sitting height. Participants aged <24 months at baseline and >=24 months at Week 52, body length and crown to rump length take precedence.

Outcome measures

Measure	Cohort 1: Placebo n=16 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=19 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=7 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=12 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=8 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide n=11 Participants Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Upper body length	3.04 cm Standard Deviation 1.52	3.54 cm Standard Deviation 1.81	5.45 cm Standard Deviation 1.75	5.20 cm Standard Deviation 1.50	6.58 cm Standard Deviation 0.99	6.75 cm Standard Deviation 0.86
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Head Circumference	0.68 cm Standard Deviation 0.66	0.74 cm Standard Deviation 0.49	2.29 cm Standard Deviation 1.28	3.10 cm Standard Deviation 1.45	5.35 cm Standard Deviation 0.71	6.29 cm Standard Deviation 0.81
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Arm Span	4.86 cm Standard Deviation 1.99	5.82 cm Standard Deviation 3.65	7.13 cm Standard Deviation 1.59	7.22 cm Standard Deviation 1.45	8.22 cm Standard Deviation 1.93	8.99 cm Standard Deviation 4.77
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Upper Arm Length	1.02 cm Standard Deviation 1.13	0.77 cm Standard Deviation 0.96	1.08 cm Standard Deviation 0.93	1.44 cm Standard Deviation 1.26	1.95 cm Standard Deviation 1.23	1.44 cm Standard Deviation 1.33
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Lower Arm (Forearm) Length	0.49 cm Standard Deviation 0.96	0.79 cm Standard Deviation 0.90	1.78 cm Standard Deviation 0.44	1.57 cm Standard Deviation 0.98	1.66 cm Standard Deviation 0.82	1.49 cm Standard Deviation 0.79
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Lower Body Length	2.41 cm Standard Deviation 1.31	2.89 cm Standard Deviation 1.99	2.39 cm Standard Deviation 1.27	3.79 cm Standard Deviation 1.56	3.86 cm Standard Deviation 1.55	4.41 cm Standard Deviation 1.53
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Upper Leg Length (Thigh)	0.82 cm Standard Deviation 1.75	1.55 cm Standard Deviation 1.46	0.38 cm Standard Deviation 1.71	1.10 cm Standard Deviation 1.42	1.98 cm Standard Deviation 2.21	1.93 cm Standard Deviation 1.65
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Knee to Heel Length	1.52 cm Standard Deviation 0.76	2.21 cm Standard Deviation 0.67	2.70 cm Standard Deviation 0.75	2.29 cm Standard Deviation 1.91	2.93 cm Standard Deviation 0.68	3.12 cm Standard Deviation 0.85
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 Tibial Length	0.85 cm Standard Deviation 0.69	1.16 cm Standard Deviation 1.35	1.97 cm Standard Deviation 1.49	1.99 cm Standard Deviation 0.80	1.83 cm Standard Deviation 0.88	1.39 cm Standard Deviation 0.77

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population. Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available

For Height: subjects aged < 24 months, body length takes precedence over standing height. Subjects aged < 24 months at baseline and >= 24 months at Week 52, body length takes precedence.

Outcome measures

Measure	Cohort 1: Placebo n=16 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=19 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=7 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=10 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=8 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide n=11 Participants Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 Upper Arm Length to Lower Arm(Forearm)Length Ratio	0.05 Ratio Standard Deviation 0.15	0.00 Ratio Standard Deviation 0.12	-0.09 Ratio Standard Deviation 0.06	0.01 Ratio Standard Deviation 0.10	0.02 Ratio Standard Deviation 0.11	-0.01 Ratio Standard Deviation 0.12
Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 Upper Leg Length(Thigh)-Knee to Heel Length Ratio	-0.01 Ratio Standard Deviation 0.08	0.01 Ratio Standard Deviation 0.07	-0.09 Ratio Standard Deviation 0.10	-0.03 Ratio Standard Deviation 0.08	0.01 Ratio Standard Deviation 0.16	-0.02 Ratio Standard Deviation 0.11
Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 Upper Leg Length (Thigh) to Tibial Length Ratio	0.00 Ratio Standard Deviation 0.12	0.02 Ratio Standard Deviation 0.17	-0.16 Ratio Standard Deviation 0.24	-0.10 Ratio Standard Deviation 0.07	0.00 Ratio Standard Deviation 0.29	0.04 Ratio Standard Deviation 0.22
Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 Arm Span to Standing Height Ratio	0.00 Ratio Standard Deviation 0.02	0.00 Ratio Standard Deviation 0.06	0.00 Ratio Standard Deviation 0.02	-0.01 Ratio Standard Deviation 0.02	-0.01 Ratio Standard Deviation 0.04	-0.02 Ratio Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population. Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available.

Body Mass Index (BMI): For height used for BMI calculation, participants aged < 24 months, body length takes precedence over standing height. Participants aged < 24 months at baseline and >= 24 months at Week 52, body length takes precedence.

Outcome measures

Measure	Cohort 1: Placebo n=16 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=19 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=7 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=12 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=8 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide n=11 Participants Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Body Mass Index (BMI) at Week 52	0.20 kg/m^2 Standard Deviation 1.34	-0.45 kg/m^2 Standard Deviation 0.94	0.55 kg/m^2 Standard Deviation 1.17	0.08 kg/m^2 Standard Deviation 0.75	0.74 kg/m^2 Standard Deviation 1.70	0.94 kg/m^2 Standard Deviation 1.42

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population.

The body mass index (BMI) Z-score represents the participant's BMI converted to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. The weight Z-score of 0 represents the mean BMI for age and sex of the reference population. A positive BMI Z-score means BMI is above the mean BMI for the average stature population of the same sex and age and a negative BMI Z-Score means BMI is below the mean BMI for the average stature population of the same sex and age.

BMI Z-scores are derived only for participants aged 24 months or older, the change from baseline to Week 52 in BMI Z-score is summarized for Cohort 1 only as no participants in Cohort 2 or Cohort 3 were 24 months at baseline.

Outcome measures

Measure	Cohort 1: Placebo n=16 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=19 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in BMI Z-score at Week 52	-0.12 Z-Score Standard Deviation 0.48	-0.18 Z-Score Standard Deviation 0.65	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available

The weight Z-score represents the participant's weight converted to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. The weight Z-score of 0 represents the mean weight for age and sex of the reference population. A positive weight Z-score means weight is above the mean weight for the average stature population of the same sex and age and a negative weight Z-Score means weight is below the mean weight for the average stature population of the same sex and age.

Outcome measures

Measure	Cohort 1: Placebo n=16 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=19 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=7 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=12 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=8 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide n=11 Participants Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Weight Z-score at Week 52	0.14 Z-score Standard Deviation 0.44	0.14 Z-score Standard Deviation 0.42	0.74 Z-score Standard Deviation 0.82	0.70 Z-score Standard Deviation 0.64	-0.81 Z-score Standard Deviation 0.49	-0.66 Z-score Standard Deviation 0.77

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population. Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health).

Outcome measures

Measure	Cohort 1: Placebo n=14 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=17 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=7 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=12 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=8 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide n=10 Participants Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Pain Score	-1.19 Score on a scale Standard Deviation 20.37	-1.47 Score on a scale Standard Deviation 18.22	-1.19 Score on a scale Standard Deviation 18.90	-7.64 Score on a scale Standard Deviation 27.63	-4.69 Score on a scale Standard Deviation 27.77	2.50 Score on a scale Standard Deviation 22.58
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Overall Health Score	3.75 Score on a scale Standard Deviation 17.60	4.33 Score on a scale Standard Deviation 15.10	-5.00 Score on a scale Standard Deviation 15.41	-3.50 Score on a scale Standard Deviation 14.15	-5.00 Score on a scale Standard Deviation 7.75	0.50 Score on a scale Standard Deviation 13.01
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Physical Abilities Score	-6.01 Score on a scale Standard Deviation 9.83	8.82 Score on a scale Standard Deviation 23.06	3.36 Score on a scale Standard Deviation 8.62	1.30 Score on a scale Standard Deviation 16.05	2.35 Score on a scale Standard Deviation 29.29	-15.91 Score on a scale Standard Deviation 22.74
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Growth and Development Scores	4.82 Score on a scale Standard Deviation 11.62	4.34 Score on a scale Standard Deviation 9.40	-0.71 Score on a scale Standard Deviation 8.75	1.46 Score on a scale Standard Deviation 26.01	3.57 Score on a scale Standard Deviation 6.35	-3.50 Score on a scale Standard Deviation 13.19
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Temperament and mood Score	4.79 Score on a scale Standard Deviation 9.60	0.54 Score on a scale Standard Deviation 5.40	0.66 Score on a scale Standard Deviation 7.18	-0.49 Score on a scale Standard Deviation 9.78	-2.43 Score on a scale Standard Deviation 6.76	4.62 Score on a scale Standard Deviation 10.48
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Global health perceptions score	-1.07 Score on a scale Standard Deviation 15.43	2.24 Score on a scale Standard Deviation 12.37	-2.73 Score on a scale Standard Deviation 11.29	-4.55 Score on a scale Standard Deviation 12.18	-2.84 Score on a scale Standard Deviation 13.62	0.50 Score on a scale Standard Deviation 17.11
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Parental impact emotional score	2.04 Score on a scale Standard Deviation 23.13	-0.84 Score on a scale Standard Deviation 8.89	0.51 Score on a scale Standard Deviation 14.64	-6.85 Score on a scale Standard Deviation 11.94	9.82 Score on a scale Standard Deviation 20.89	-2.50 Score on a scale Standard Deviation 19.05
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Parental Impact Time Score	9.52 Score on a scale Standard Deviation 29.06	4.76 Score on a scale Standard Deviation 10.78	-8.05 Score on a scale Standard Deviation 19.70	-2.38 Score on a scale Standard Deviation 35.61	-10.7 Score on a scale Standard Deviation 17.59	2.38 Score on a scale Standard Deviation 14.93
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 Family Cohesion Score	1.79 Score on a scale Standard Deviation 13.53	-1.25 Score on a scale Standard Deviation 10.72	0.00 Score on a scale Standard Deviation 15.00	-7.08 Score on a scale Standard Deviation 28.08	-3.13 Score on a scale Standard Deviation 8.84	-4.50 Score on a scale Standard Deviation 15.54

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Full Analysis Set. Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health).

The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable.

Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed.

Outcome measures

Measure	Cohort 1: Placebo n=13 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=17 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=5 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=8 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=1 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in ITQoL-Behavior Scores at Week 52	2.73 Score on a scale Standard Deviation 23.36	0.37 Score on a scale Standard Deviation 9.50	1.74 Score on a scale Standard Deviation 13.60	-3.39 Score on a scale Standard Deviation 7.46	0.00 Score on a scale Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD values are proposed as NA.	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population. Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global behaviour.

The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable.

Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed.

Outcome measures

Measure	Cohort 1: Placebo n=13 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=17 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=5 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=9 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=1 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in ITQoL-Global Behavior Scores at Week 52	1.15 Score on a scale Standard Deviation 21.42	0.29 Score on a scale Standard Deviation 18.58	3.00 Score on a scale Standard Deviation 12.55	-10.56 Score on a scale Standard Deviation 21.71	-15.00 Score on a scale Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD values are proposed as NA.	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population. Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global health perceptions.

The number of subjects assessed in Cohort 3 Placebo and Cohort 3 vosoritide are 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/baseline. Hence, Mean and Standard Deviation (SD) are not applicable.

Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed.

Outcome measures

Measure	Cohort 1: Placebo n=12 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=17 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=5 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=8 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in ITQoL-Getting On With Other Score at Week 52	7.78 Score on a scale Standard Deviation 17.18	1.74 Score on a scale Standard Deviation 8.88	2.33 Score on a scale Standard Deviation 7.22	0.82 Score on a scale Standard Deviation 5.35	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population. Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global change in health.

The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable.

Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed.

Outcome measures

Measure	Cohort 1: Placebo n=13 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=16 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=5 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=6 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=1 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in ITQoL-Health Score at Week 52	0.08 Score on a scale Standard Deviation 0.64	0.13 Score on a scale Standard Deviation 0.62	-0.60 Score on a scale Standard Deviation 1.34	0.33 Score on a scale Standard Deviation 0.52	0.00 Score on a scale Standard Deviation NA As the number of subjects assessed in this category is only 1, standard deviation (SD) is not applicable. Hence SD value is proposed as NA.	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

The Pediatric Functional Independence Measure-II (WeeFIM®-II) is designed to measure functional independence of children between the ages of 6 months & 18 yrs who have physical or general developmental limitations. The WeeFIM-II is comprised of 3 domains that are rated by clinicians based on information obtained from parents/caregivers (self-care [score range 8 to 56], mobility [score range 8 to 35], & cognition [score range 8 to 35]) & provides a total score between 18 (worst) & 126 (Best). Higher score reflects higher level of independence.

Performance of a child on each of individual items within WeeFIM is assigned to one of seven levels on an ordinal scale that represent function from complete & modified independence (levels 7 & 6) without a helping person to modified & complete dependence (levels 5 to 1) with a helping person.

Functional Independence Measure (Wee-FIM-II) is only validated in children ages 6 months to 18 yrs. Therefore results for Cohort 3 is not summarized.

Outcome measures

Measure	Cohort 1: Placebo n=14 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=19 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=6 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=11 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 WeeFIM-II Total Score	11.2 Score on a scale Standard Deviation 11.1	14.7 Score on a scale Standard Deviation 17.3	16.2 Score on a scale Standard Deviation 14.6	16.5 Score on a scale Standard Deviation 28.1	—	—
Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 WeeFIM : Self-Care Score	6.4 Score on a scale Standard Deviation 6.0	6.6 Score on a scale Standard Deviation 7.2	3.7 Score on a scale Standard Deviation 2.3	5.6 Score on a scale Standard Deviation 14.1	—	—
Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 WeeFIM: Mobility Score	2.2 Score on a scale Standard Deviation 3.4	4.5 Score on a scale Standard Deviation 5.6	7.0 Score on a scale Standard Deviation 7.5	6.7 Score on a scale Standard Deviation 9.4	—	—
Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 WeeFIM: Cognitive Score	2.6 Score on a scale Standard Deviation 4.0	3.6 Score on a scale Standard Deviation 6.0	5.5 Score on a scale Standard Deviation 7.6	4.2 Score on a scale Standard Deviation 8.4	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

BSID-III is performance-based clinician-reported outcome assessment for use in children from 1 to 42 months (1 month to 3.5 years). individually administered by the trained clinician to the participant/child

Scales include Cognitive subscale, Receptive and Expressive subscales, and Gross and Fine Motor subscales. The two language scales make up a composite Language Scale score and the Gross and Fine Motor subscales yield a composite Motor Scale score. In addition, there is a Social-Emotional Scale and Adaptive Behavior Scale, which is a questionnaire read and completed by parent or caregiver. Scores range from 0 to 2, and indicate mastery (2), emerging (1) or zero (not present)

Each (sub)scale yields a total raw score, standardized according to the participant's chronological age (scaled scores)

Outcome measures

Measure	Cohort 1: Placebo n=2 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=4 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=4 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=9 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=6 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide n=9 Participants Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Motor Composite Score	-2.0 Score on a scale Standard Deviation 5.7	4.8 Score on a scale Standard Deviation 11.5	12.0 Score on a scale Standard Deviation 17.5	-2.3 Score on a scale Standard Deviation 12.3	5.4 Score on a scale Standard Deviation 22.2	11.1 Score on a scale Standard Deviation 18.1
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Cognitive scaled score	-1.0 Score on a scale Standard Deviation 2.8	-0.5 Score on a scale Standard Deviation 1.7	3.3 Score on a scale Standard Deviation 4.9	0.6 Score on a scale Standard Deviation 3.2	1.5 Score on a scale Standard Deviation 1.9	2.1 Score on a scale Standard Deviation 4.4
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Cognitive composite score	-5.0 Score on a scale Standard Deviation 14.1	-2.5 Score on a scale Standard Deviation 8.7	16.7 Score on a scale Standard Deviation 24.7	3.1 Score on a scale Standard Deviation 16.0	7.5 Score on a scale Standard Deviation 9.4	10.6 Score on a scale Standard Deviation 22.1
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Receptive communication language scaled score	-1.0 Score on a scale Standard Deviation 0.0	-1.8 Score on a scale Standard Deviation 2.5	3.3 Score on a scale Standard Deviation 4.0	1.0 Score on a scale Standard Deviation 1.2	-3.0 Score on a scale Standard Deviation 2.1	0.7 Score on a scale Standard Deviation 5.2
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Expressive communication language scaled score	2.5 Score on a scale Standard Deviation 0.7	0.3 Score on a scale Standard Deviation 1.3	2.8 Score on a scale Standard Deviation 2.9	-0.1 Score on a scale Standard Deviation 2.2	-1.8 Score on a scale Standard Deviation 1.6	-0.1 Score on a scale Standard Deviation 3.3
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Language sum of scaled score	1.5 Score on a scale Standard Deviation 0.7	-1.5 Score on a scale Standard Deviation 3.3	6.0 Score on a scale Standard Deviation 5.2	1.8 Score on a scale Standard Deviation 4.0	-7.3 Score on a scale Standard Deviation 6.4	-0.3 Score on a scale Standard Deviation 6.6
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Language composite score	4.5 Score on a scale Standard Deviation 2.1	-4.5 Score on a scale Standard Deviation 9.9	17.8 Score on a scale Standard Deviation 15.2	5.3 Score on a scale Standard Deviation 12.1	-13.4 Score on a scale Standard Deviation 5.8	-0.9 Score on a scale Standard Deviation 19.5
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Fine motor scaled score	-0.5 Score on a scale Standard Deviation 3.5	0.0 Score on a scale Standard Deviation 2.9	1.5 Score on a scale Standard Deviation 3.3	-2.1 Score on a scale Standard Deviation 2.5	2.2 Score on a scale Standard Deviation 4.8	2.6 Score on a scale Standard Deviation 2.7
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 Gross motor scaled score	0.0 Score on a scale Standard Deviation 5.7	1.0 Score on a scale Standard Deviation 0.8	2.8 Score on a scale Standard Deviation 3.2	1.3 Score on a scale Standard Deviation 2.8	-0.2 Score on a scale Standard Deviation 3.1	0.1 Score on a scale Standard Deviation 3.0

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

The CBCL is used as a screening tool for emotional or behavioral problems, measuring initial behavior severity, tracking changes in behavioral problems over the course of treatment, and treatment planning. The CBCL 1.5-5 years old consists of 100 questions, scored on a three-point Likert scale (0=Not True (as far as you know), 1= Somewhat or Sometimes True, 2=Very True or Often True). The scores for each individual question within a domain are summed to give a domain score. The CBCL uses a normative sample to create standard scores, which are scaled so that 50 is average with a standard deviation of 10, where higher scores indicate more emotional or behavioral issues.

CBCL was waived for children < 18 months old. Therefore results for Cohort 3 is not summarized.

Outcome measures

Measure	Cohort 1: Placebo n=15 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=18 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=4 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=5 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 CBCL Pre-School : Emotionally Reactive Total	-0.2 Score on a scale Standard Deviation 1.5	0.1 Score on a scale Standard Deviation 1.4	1.0 Score on a scale Standard Deviation 2.0	1.0 Score on a scale Standard Deviation 3.9	—	—
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 CBCL Pre-School : Anxious/Depressed Total	0.3 Score on a scale Standard Deviation 1.7	0.2 Score on a scale Standard Deviation 1.4	0.0 Score on a scale Standard Deviation 2.2	0.8 Score on a scale Standard Deviation 3.1	—	—
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 CBCL Pre-School : Withdrawn Total	-0.6 Score on a scale Standard Deviation 1.7	0.6 Score on a scale Standard Deviation 1.5	0.8 Score on a scale Standard Deviation 2.2	-0.2 Score on a scale Standard Deviation 1.6	—	—
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 CBCL Pre-School : Somatic Complaints Total	0.1 Score on a scale Standard Deviation 1.7	0.3 Score on a scale Standard Deviation 1.0	0.5 Score on a scale Standard Deviation 1.0	1.8 Score on a scale Standard Deviation 4.1	—	—
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 CBCL Pre-School : Sleep Problems Total	-0.3 Score on a scale Standard Deviation 3.2	0.1 Score on a scale Standard Deviation 1.9	-0.3 Score on a scale Standard Deviation 1.7	1.4 Score on a scale Standard Deviation 4.3	—	—
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 CBCL Pre-School : Attention Problems Total	-0.1 Score on a scale Standard Deviation 1.9	-0.1 Score on a scale Standard Deviation 1.6	-0.3 Score on a scale Standard Deviation 1.0	-0.2 Score on a scale Standard Deviation 2.0	—	—
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 CBCL Pre-School : Aggressive Behavior Total	-1.1 Score on a scale Standard Deviation 2.4	0.3 Score on a scale Standard Deviation 4.1	-0.8 Score on a scale Standard Deviation 1.5	-0.4 Score on a scale Standard Deviation 2.7	—	—
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 CBCL Pre-School : Total Problems Total	-3.0 Score on a scale Standard Deviation 13.0	2.8 Score on a scale Standard Deviation 11.7	-2.3 Score on a scale Standard Deviation 6.0	3.6 Score on a scale Standard Deviation 23.2	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=40 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=27 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Left Femur Length	2.29 cm Standard Deviation 0.58	2.01 cm Standard Deviation 0.62	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Right Femur Length	2.35 cm Standard Deviation 0.49	2.20 cm Standard Deviation 0.73	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Left Fibula Length	2.00 cm Standard Deviation 0.61	1.97 cm Standard Deviation 0.69	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Right Fibula Length	2.00 cm Standard Deviation 0.64	1.89 cm Standard Deviation 0.75	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Left Tibia Length	1.92 cm Standard Deviation 0.55	1.69 cm Standard Deviation 0.70	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Right Tibia Length	1.96 cm Standard Deviation 0.57	1.68 cm Standard Deviation 0.77	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Left Distance Between Ankle Joint and Distal Growth Plate of Fibula	-0.02 cm Standard Deviation 0.23	0.07 cm Standard Deviation 0.23	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Right Distance Between Ankle Joint and Distal Growth Plate of Fibula	-0.05 cm Standard Deviation 0.23	0.05 cm Standard Deviation 0.22	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Left Lower Extremity	6.02 cm Standard Deviation 6.67	3.87 cm Standard Deviation 1.56	—	—	—	—
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 Right Lower Extremity	6.08 cm Standard Deviation 6.54	4.26 cm Standard Deviation 1.85	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available

Outcome measures

Measure	Cohort 1: Placebo n=39 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=27 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Bilateral X-rays of Left/Right Tibia Bowing Angle at Week 52 Left Tibia Bowing Angle	-0.97 Degrees Standard Deviation 5.88	1.07 Degrees Standard Deviation 5.38	—	—	—	—
Change From Baseline in Bilateral X-rays of Left/Right Tibia Bowing Angle at Week 52 Right Tibia Bowing Angle	-2.34 Degrees Standard Deviation 5.37	-0.93 Degrees Standard Deviation 5.54	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52 End point timeframe:

Population: Safety Population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=17 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=14 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Bilateral X-rays of Left Femur Length (cm) to Tibia Length (cm) Ratio and Right Femur Length (cm) to Tibia Length (cm) Ratio at Week 52 Left Femur Length (cm) to Tibia Length (cm) Ratio	-0.03 Ratio Standard Deviation 0.06	-0.05 Ratio Standard Deviation 0.05	—	—	—	—
Change From Baseline in Bilateral X-rays of Left Femur Length (cm) to Tibia Length (cm) Ratio and Right Femur Length (cm) to Tibia Length (cm) Ratio at Week 52 Right Femur Length (cm) to Tibia Length (cm) Ratio	-0.05 Ratio Standard Deviation 0.06	-0.02 Ratio Standard Deviation 0.03	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=40 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=27 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in Bilateral X-rays of Left Tibia Length (cm) to Fibula Length (cm) Ratio & Right Tibia Length (cm) to Fibula Length (cm) Ratio at Week 52 Left Tibia Length (cm) to Fibula Length (cm) Ratio	-0.02 Ratio Standard Deviation 0.04	-0.04 Ratio Standard Deviation 0.04	—	—	—	—
Change From Baseline in Bilateral X-rays of Left Tibia Length (cm) to Fibula Length (cm) Ratio & Right Tibia Length (cm) to Fibula Length (cm) Ratio at Week 52 Right Tibia Length (cm) to Fibula Length(cm) Ratio	-0.02 Ratio Standard Deviation 0.05	-0.03 Ratio Standard Deviation 0.04	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=40 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=27 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Medial Height Ratio (L1)	-0.04 Ratio Standard Deviation 0.16	-0.04 Ratio Standard Deviation 0.20	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Medial Height Ratio (L2)	-0.06 Ratio Standard Deviation 0.16	-0.07 Ratio Standard Deviation 0.16	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Medial Height Ratio (L3)	-0.02 Ratio Standard Deviation 0.19	0.04 Ratio Standard Deviation 0.09	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Medial Height Ratio (L4)	0.02 Ratio Standard Deviation 0.12	-0.01 Ratio Standard Deviation 0.11	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Medial Height Ratio (L5)	-0.02 Ratio Standard Deviation 0.15	0.04 Ratio Standard Deviation 0.17	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Posterior Height Ratio (L1)	-0.03 Ratio Standard Deviation 0.13	-0.08 Ratio Standard Deviation 0.17	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Posterior Height Ratio (L2)	-0.02 Ratio Standard Deviation 0.13	-0.03 Ratio Standard Deviation 0.12	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Posterior Height Ratio (L3)	-0.01 Ratio Standard Deviation 0.16	0.04 Ratio Standard Deviation 0.12	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Posterior Height Ratio (L4)	0.03 Ratio Standard Deviation 0.11	0.02 Ratio Standard Deviation 0.13	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Anterior Height to Posterior Height Ratio (L5)	0.01 Ratio Standard Deviation 0.13	0.02 Ratio Standard Deviation 0.15	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Medial Height to Posterior Height Ratio (L1)	-0.01 Ratio Standard Deviation 0.15	-0.04 Ratio Standard Deviation 0.12	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Medial Height to Posterior Height Ratio (L2)	0.05 Ratio Standard Deviation 0.11	0.03 Ratio Standard Deviation 0.09	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Medial Height to Posterior Height Ratio (L3)	-0.02 Ratio Standard Deviation 0.10	-0.02 Ratio Standard Deviation 0.10	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Medial Height to Posterior Height Ratio (L4)	-0.03 Ratio Standard Deviation 0.13	0.04 Ratio Standard Deviation 0.10	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 Medial Height to Posterior Height Ratio (L5)	0.02 Ratio Standard Deviation 0.16	-0.04 Ratio Standard Deviation 0.21	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=40 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=27 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 Transverse Diameter (L1)	0.12 cm Standard Deviation 0.17	0.12 cm Standard Deviation 0.11	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 Transverse Diameter (L2)	0.12 cm Standard Deviation 0.16	0.09 cm Standard Deviation 0.13	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 Transverse Diameter (L3)	0.08 cm Standard Deviation 0.15	0.09 cm Standard Deviation 0.12	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 Transverse Diameter (L4)	0.09 cm Standard Deviation 0.13	0.06 cm Standard Deviation 0.11	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 Transverse Diameter (L5)	0.10 cm Standard Deviation 0.13	0.05 cm Standard Deviation 0.14	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on subjects with available measurements at both time points. Overall no. of participants analyzed (N) is greater than no. analyzed for Placebo, as different participants missed for different variables (Ex:1 subject missed sagittal width L1,L2,L3, 1 subject missed sagittal width L5 \& 1 subject missed sagittal width L4 \& L5. Therefore, n for sagittal width L1,L2,L3,L4 \& L5 are 26,26,26,26,25 respectively but the overall number of subjects is 27)

Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=34 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=27 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 Sagittal Width (L1)	0.07 cm Standard Deviation 0.26	0.00 cm Standard Deviation 0.22	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 Sagittal Width (L2)	0.05 cm Standard Deviation 0.18	0.01 cm Standard Deviation 0.18	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 Sagittal Width (L3)	0.08 cm Standard Deviation 0.20	0.04 cm Standard Deviation 0.19	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 Sagittal Width (L4)	0.16 cm Standard Deviation 0.24	0.03 cm Standard Deviation 0.16	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 Sagittal Width (L5)	0.13 cm Standard Deviation 0.34	0.06 cm Standard Deviation 0.26	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=40 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=27 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 Sacral Tilt	10.6 Degree Standard Deviation 13.2	5.7 Degree Standard Deviation 15.9	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 Lordosis Angle	12.5 Degree Standard Deviation 17.4	8.4 Degree Standard Deviation 14.2	—	—	—	—
Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 Kyphosis Angle	-2.2 Degree Standard Deviation 13.9	-2.1 Degree Standard Deviation 10.3	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Percentages were calculated using the total number of subjects in the safety population (N for each treatment group) as the denominator.

All increases are comparing results at Week 52 relative to the baseline assessment.

Outcome measures

Measure	Cohort 1: Placebo n=37 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=21 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 Increase in sacral tilt (deg) >=10	24 Number of participants	10 Number of participants	—	—	—	—
Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 Increase in lordosis angle (deg) >=5 to <10	5 Number of participants	1 Number of participants	—	—	—	—
Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 Increase in lordosis angle (deg) >=10	19 Number of participants	14 Number of participants	—	—	—	—
Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 Increase in kyphosis angle (deg) >=5 to <10	3 Number of participants	2 Number of participants	—	—	—	—
Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 Increase in kyphosis angle (deg) >=10	9 Number of participants	4 Number of participants	—	—	—	—
Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 Increase in sacral tilt (deg) >=5 to <10	3 Number of participants	6 Number of participants	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=35 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=25 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Volume of Face	80.527 cm^3 Standard Deviation 59.211	78.107 cm^3 Standard Deviation 33.369	—	—	—	—
MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Volume of Sinus	2.362 cm^3 Standard Deviation 3.578	1.195 cm^3 Standard Deviation 3.769	—	—	—	—
MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Volume of Calvarium	213.075 cm^3 Standard Deviation 202.415	183.427 cm^3 Standard Deviation 183.210	—	—	—	—
MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Whole Brain Total Volume	175.399 cm^3 Standard Deviation 158.088	146.247 cm^3 Standard Deviation 115.274	—	—	—	—
MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Ventricles Total Volume	11.394 cm^3 Standard Deviation 20.416	8.515 cm^3 Standard Deviation 16.325	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety Population Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available

Outcome measures

Measure	Cohort 1: Placebo n=35 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=25 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Volume of Face	20.79 percent change Standard Deviation 18.46	19.18 percent change Standard Deviation 12.22	—	—	—	—
MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Volume of sinus	72.33 percent change Standard Deviation 100.93	81.97 percent change Standard Deviation 169.74	—	—	—	—
MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Volume of Calvarium	19.41 percent change Standard Deviation 21.73	16.50 percent change Standard Deviation 19.82	—	—	—	—
MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Whole Brain Total Volume	20.58 percent change Standard Deviation 21.29	16.89 percent change Standard Deviation 17.22	—	—	—	—
MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. Ventricles Total Volume	33.44 percent change Standard Deviation 52.69	30.85 percent change Standard Deviation 50.65	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=35 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=25 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
MRI Parameter: Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level Area of Foramen Magnum	0.021 cm^2 Standard Deviation 0.342	0.060 cm^2 Standard Deviation 0.203	—	—	—	—
MRI Parameter: Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level Area of Spinal Cord at the Foramen Magnum Level	0.011 cm^2 Standard Deviation 0.197	0.072 cm^2 Standard Deviation 0.163	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety Population. Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=35 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=25 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
MRI Parameter: Percentage Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level Area of Foramen Magnum	9.19 Percent change Standard Deviation 47.36	7.50 Percent change Standard Deviation 19.88	—	—	—	—
MRI Parameter: Percentage Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level Area of spinal cord at the foramen magnum level	7.51 Percent change Standard Deviation 33.14	19.60 Percent change Standard Deviation 44.26	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population. Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=35 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=25 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus Ratio of face volume to calvarium	0.002 Ratio Standard Deviation 0.031	0.003 Ratio Standard Deviation 0.033	—	—	—	—
MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus Ratio of area of spinal cord to foramen magnum	0.005 Ratio Standard Deviation 0.120	0.037 Ratio Standard Deviation 0.100	—	—	—	—
MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus Ratio of face volume to sinus	-6.798 Ratio Standard Deviation 175.646	14.505 Ratio Standard Deviation 284.950	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety Population. Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=35 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=25 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus Ratio of Face Volume to Calvarium	0.78 Percent change Standard Deviation 9.06	1.31 Percent change Standard Deviation 10.07	—	—	—	—
MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus Ratio of Area of Spinal Cord to Foramen Magnum	2.86 Percent change Standard Deviation 23.40	9.50 Percent change Standard Deviation 22.68	—	—	—	—
MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus Ratio of face volume to sinus	-5.37 Percent change Standard Deviation 60.83	92.24 Percent change Standard Deviation 341.33	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=26 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=20 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Dual X Ray Absorptiometry (DEXA) Parameter: Change From Baseline to Week 52 for Whole Body Less Head Bone Mineral Content (BMC) GE - Lunar Prodigy: Whole Body Less Head BMC	55.87 gm Standard Deviation 14.68	50.26 gm Standard Deviation 17.44	—	—	—	—
Dual X Ray Absorptiometry (DEXA) Parameter: Change From Baseline to Week 52 for Whole Body Less Head Bone Mineral Content (BMC) Hologic Discovery Horizon Whole Body Less Head BMC	44.61 gm Standard Deviation 12.62	47.19 gm Standard Deviation 12.55	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=26 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=20 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
DEXA Parameter: Change From Baseline to Week 52 of Whole Body Less Head Bone Mineral Density (BMD) GE - Lunar Prodigy Whole Body Less Head BMD	0.04 g/cm^2 Standard Deviation 0.02	0.05 g/cm^2 Standard Deviation 0.03	—	—	—	—
DEXA Parameter: Change From Baseline to Week 52 of Whole Body Less Head Bone Mineral Density (BMD) Hologic Discovery Horizon Whole Body Less Head BMD	0.03 g/cm^2 Standard Deviation 0.01	0.04 g/cm^2 Standard Deviation 0.02	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=26 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=20 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMC GE - Lunar Prodigy Whole Body BMC	96.85 gm Standard Deviation 39.82	98.99 gm Standard Deviation 32.45	—	—	—	—
DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMC Hologic - Discovery Horizon Whole Body BMC	87.97 gm Standard Deviation 32.35	101.33 gm Standard Deviation 33.34	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=36 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=23 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMC GE - Lunar Prodigy Lumbar Spine BMC	2.73 gm Standard Deviation 0.83	2.09 gm Standard Deviation 0.97	—	—	—	—
DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMC Hologic - Discovery Horizon Lumbar Spine BMC	2.19 gm Standard Deviation 0.68	1.94 gm Standard Deviation 0.72	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=26 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=20 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMD GE - Lunar Prodigy Whole Body BMD	0.06 g/cm^2 Standard Deviation 0.06	0.07 g/cm^2 Standard Deviation 0.04	—	—	—	—
DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMD Hologic - Discovery Horizon Whole Body BMD	0.05 g/cm^2 Standard Deviation 0.02	0.07 g/cm^2 Standard Deviation 0.03	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Outcome measures

Measure	Cohort 1: Placebo n=36 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=23 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMD GE - Lunar Prodigy Lumbar Spine BMD	0.07 g/cm^2 Standard Deviation 0.04	0.05 g/cm^2 Standard Deviation 0.03	—	—	—	—
DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMD Hologic - Discovery Horizon Lumbar Spine BMD	0.05 g/cm^2 Standard Deviation 0.03	0.06 g/cm^2 Standard Deviation 0.04	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Hologic - Discovery Horizon Whole Body BMD Z-Score.

Change in whole body bone mineral density (BMD) Z-score from baseline at 52 weeks indicates whether there has been a positive or negative change in BMD using a z-score generated by converting the participants BMD to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. A whole body BMD Z-score <-2 SD can indicate low bone density in children. The Whole Body BMD (bone mineral density) z-score compares the BMD to the average bone density of people of the same age, and sex as a comparator. A Z-score less than 0 means that the participant has a lower BMD than people in the same age and sex group, and could indicate a risk of osteopenia or osteoporosis.

Outcome measures

Measure	Cohort 1: Placebo n=6 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=4 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline to Week 52 in Whole Body BMD Z-score	-0.20 Z-score Standard Deviation 0.35	0.30 Z-score Standard Deviation 0.47	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Safety population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.

Hologic - Discovery Horizon Lumbar Spine BMD Z-Score

Change in lumbar spine bone mineral density (BMD) Z-score from baseline at 52 weeks indicates whether there has been a positive or negative change in BMD using a z-score generated by converting the participants lumbar spine BMD to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. A BMD Z-score <-2 SD can indicate low bone density in the lumbar spine in children. The Lumbar Spine BMD (bone mineral density) z-score compares the BMD in the lumbar spine to the average spinal bone density of people of the same age, and sex as a comparator. A Z-score less than 0 means that the participant has a lower BMD than people in the same age and sex group, and could indicate a risk of osteopenia or osteoporosis of the spine.

Outcome measures

Measure	Cohort 1: Placebo n=7 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=4 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change From Baseline to Week 52 in Lumbar Spine BMD Z-Score	0.17 Z-score Standard Deviation 0.24	0.03 Z-score Standard Deviation 0.45	—	—	—	—

SECONDARY outcome

Timeframe: At Day 1, Week 3, Week 13, Week 26, Week 52, & Ever Positive.

Population: FAS population

Number of participants with Incidence of Antibody Positivity at Scheduled Visits for : total antibody (TAb), Neutralizing antibodies (NAb), atrial natriuretic peptide (ANP), B-type Natriuretic Peptide (BNP) & C-type natriuretic peptide (CNP).

TAb Titer Positive, NAb Titer Positive, ANP Reactivity Positive, BNP Reactivity Positive & CNP Reactivity Positive.

Day 1 is the baseline assessment result taken prior to first dose of study drug.

Ever Positive = the number of participants with at least one positive sample result.

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits TAb Titer Positive: Day 1	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits TAb Titer Positive: Week 3	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits TAb Titer Positive: Week 13	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits TAb Titer Positive: Week 26	2 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits TAb Titer Positive: Week 52	8 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits TAb Titer Ever Positive	8 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits NAb Titer Positive: Day 1	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits NAb Titer Positive: Week 3	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits NAb Titer Positive: Week 13	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits NAb Titer Positive: Week 26	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits NAb Titer Positive: Week 52	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits NAb Titer Ever Positive	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits ANP Reactivity Positive: Day 1	3 participants	5 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits ANP Reactivity Positive: Week 3	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits ANP Reactivity Positive: Week 13	1 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits ANP Reactivity Positive: Week 26	6 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits ANP Reactivity Positive: Week 52	11 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits ANP Reactivity Ever Positive	12 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits BNP Reactivity Positive: Day 1	0 participants	3 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits BNP Reactivity Positive: Week 3	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits BNP Reactivity Positive: Week 13	2 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits BNP Reactivity Positive: Week 26	3 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits BNP Reactivity Positive: Week 52	2 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits BNP Reactivity Ever Positive	3 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits CNP Reactivity Positive: Day 1	0 participants	1 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits CNP Reactivity Positive: Week 3	0 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits CNP Reactivity Positive: Week 13	1 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits CNP Reactivity Positive: Week 26	2 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits CNP Reactivity Positive: Week 52	4 participants	0 participants	—	—	—	—
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits CNP Reactivity Ever Positive	4 participants	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: At Baseline, Day 8, Week 6, Week 20, & Week 39.

Population: Safety population Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is the last measurement prior to the initiation of study drug.

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Baseline	140.28 U/L Standard Deviation 183.23	113.43 U/L Standard Deviation 33.56	—	—	—	—
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Day 8	122.32 U/L Standard Deviation 99.09	104.12 U/L Standard Deviation 29.12	—	—	—	—
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Change from baseline to Day 8	-19.39 U/L Standard Deviation 202.90	-7.67 U/L Standard Deviation 17.53	—	—	—	—
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Week 6	130.38 U/L Standard Deviation 140.08	109.46 U/L Standard Deviation 29.04	—	—	—	—
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Change from baseline to Week 6	2.63 U/L Standard Deviation 218.60	-6.17 U/L Standard Deviation 24.32	—	—	—	—
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Week 20	109.67 U/L Standard Deviation 30.88	104.46 U/L Standard Deviation 29.69	—	—	—	—
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Change from baseline to Week 20	-7.21 U/L Standard Deviation 96.94	-11.32 U/L Standard Deviation 18.19	—	—	—	—
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Week 39	108.49 U/L Standard Deviation 32.02	208.13 U/L Standard Deviation 363.56	—	—	—	—
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime BSAP: Change from baseline to Week 39	-12.21 U/L Standard Deviation 105.04	95.41 U/L Standard Deviation 352.78	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52.

Population: Safety Population Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is the last measurement prior to the initiation of study drug.

Outcome measures

Measure	Cohort 1: Placebo n=31 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=24 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Biomarker: Type II Collagen C-Telopeptides Normalized for Creatinine (CTX-II)	-9364.7 ng/ mmol Cr Standard Deviation 65244.1	-7607.6 ng/ mmol Cr Standard Deviation 54614.9	—	—	—	—

SECONDARY outcome

Timeframe: Week 52 Pre-Dose to Week 52 Maximum Post-Dose.

Population: Safety population. Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is the last measurement prior to the initiation of study drug.

Outcome measures

Measure	Cohort 1: Placebo n=33 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=21 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Biomarker: Plasma Cyclic Guanosine Monophosphate (cGMP) Change From Pre-Dose to Maximum Post-Dose at Week 52	39.079 nM Standard Deviation 25.706	9.460 nM Standard Deviation 26.307	—	—	—	—

SECONDARY outcome

Timeframe: At Baseline, Day 8, Week 6, Week 20, & Week 39.

Population: Safety Population. Change from baseline was based on subjects with available measurements at both timepoints.Overall no. of participants analyzed(N) is greater than no. analyzed for All Vosoritide, as different participants missed for different timepoints(Ex:1 of 42 participants who were part of CNP Col X BM:Baseline was not present in 42 participants who participated in CNP Col X BM:Day 8.Therefore, n for CNP Col X BM:Baseline \& CNP Col X BM:Day 8 are 42 however, overall no of subjects,N=43)

Laboratory results up to 30 days after study drug discontinuation were included.

Baseline is the last measurement prior to the initiation of study drug.

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=32 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Week 39	12249.7 pg/mL Standard Deviation 5056.5	9932.7 pg/mL Standard Deviation 4004.4	—	—	—	—
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Baseline	9833.8 pg/mL Standard Deviation 3444.7	9555.0 pg/mL Standard Deviation 4016.7	—	—	—	—
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Day 8	12093.8 pg/mL Standard Deviation 4443.8	10017.5 pg/mL Standard Deviation 3831.2	—	—	—	—
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Change from baseline to Day 8	2139.5 pg/mL Standard Deviation 3871.9	1391.3 pg/mL Standard Deviation 3354.2	—	—	—	—
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Week 6	13456.3 pg/mL Standard Deviation 4763.3	9464.8 pg/mL Standard Deviation 4243.3	—	—	—	—
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Change from baseline to Week 6	3400.3 pg/mL Standard Deviation 4554.6	200.3 pg/mL Standard Deviation 3867.5	—	—	—	—
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Week 20	12833.3 pg/mL Standard Deviation 4581.9	12064.8 pg/mL Standard Deviation 5277.3	—	—	—	—
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Change from baseline to Week 20	2928.0 pg/mL Standard Deviation 4385.9	2435.5 pg/mL Standard Deviation 4666.9	—	—	—	—
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM CNP Col X BM: Change from baseline to Week 39	2362.8 pg/mL Standard Deviation 5752.9	946.4 pg/mL Standard Deviation 3490.1	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: FAS population Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available.

Sleep-testing device was used to assess presence & severity of sleep-disordered breathing by measurement of blood oxygen(O2)saturation,pulse rate,& airflow during overnight monitoring

Episodes(Epi) of sleep apnea variables summarized as: Number(No.)of epi of apnea/hr(AI);No.of epi of hypopnea/hr(HI);No.of epi of obstructive apnea hypopneas/hr(AHI);No.of epi of obstructive apneas/hr(Obstructive Apnea Index);No.of epi of central apneas/hr(CAI);No.of desaturations/hr >=3%

AHI is a marker of obstructive sleep apnea (OSA), scored as No.of apnea or hypopnea epi/hr, with AHI <=1/hr normal, 1< AHI<=5 mild,5< AHI <=10 moderate,& AHI>10/hr severe OSA. CAI reflects cervical cord compression at cervical-medullary junction, & is No. of epi of a pause in ventilation with no associated respiratory effort, with> 5 epi/hr abnormal.O2 desaturation index measures average No. of desaturation epi/hr, defined as decrease in O2 saturation of >=3% for at least 10sec, with(<8/hr normal & >=8/hr abnormal

Outcome measures

Measure	Cohort 1: Placebo n=14 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide n=16 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo n=5 Participants Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo n=9 Participants Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo n=7 Participants Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide n=10 Participants Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
Change in Sleep Study Indices at Week 52 Apnea Hypopnea Index (AHI)	-0.54 Events per hour Standard Deviation 2.70	-1.45 Events per hour Standard Deviation 4.63	1.06 Events per hour Standard Deviation 4.80	-0.72 Events per hour Standard Deviation 1.41	1.89 Events per hour Standard Deviation 6.31	-0.94 Events per hour Standard Deviation 2.78
Change in Sleep Study Indices at Week 52 Apnea Index (AI)	-1.07 Events per hour Standard Deviation 2.12	-0.83 Events per hour Standard Deviation 1.93	0.40 Events per hour Standard Deviation 2.34	-0.71 Events per hour Standard Deviation 1.61	-1.09 Events per hour Standard Deviation 1.22	-0.36 Events per hour Standard Deviation 2.54
Change in Sleep Study Indices at Week 52 Central Apnea Index (CAI)	-1.26 Events per hour Standard Deviation 2.66	-0.74 Events per hour Standard Deviation 1.86	-0.28 Events per hour Standard Deviation 0.89	-0.71 Events per hour Standard Deviation 1.61	-1.00 Events per hour Standard Deviation 0.97	0.50 Events per hour Standard Deviation 0.92
Change in Sleep Study Indices at Week 52 Hypopnea Index (HI)	0.52 Events per hour Standard Deviation 1.35	-0.61 Events per hour Standard Deviation 3.63	0.66 Events per hour Standard Deviation 2.53	-0.01 Events per hour Standard Deviation 1.32	2.97 Events per hour Standard Deviation 5.45	-0.56 Events per hour Standard Deviation 0.54
Change in Sleep Study Indices at Week 52 Desaturation per Hour >=3%	-0.41 Events per hour Standard Deviation 1.51	-1.24 Events per hour Standard Deviation 3.98	0.98 Events per hour Standard Deviation 3.60	-0.69 Events per hour Standard Deviation 1.30	1.71 Events per hour Standard Deviation 6.63	-0.93 Events per hour Standard Deviation 2.60
Change in Sleep Study Indices at Week 52 Obstructive Index	0.19 Events per hour Standard Deviation 0.73	-0.09 Events per hour Standard Deviation 0.45	0.68 Events per hour Standard Deviation 1.52	-0.01 Events per hour Standard Deviation 0.08	-0.07 Events per hour Standard Deviation 0.64	-0.86 Events per hour Standard Deviation 2.08

SECONDARY outcome

Timeframe: At Day1, Week 13, Week 26, Week 39, & Week 52.

Population: Pharmacokinetics (PK) Population includes all sentinel and randomized participants in the safety population who have at least one evaluable PK concentration.

Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics.

PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞ excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected.

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Day 01	149000 min*pg/ml Standard Deviation 98000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 13	197000 min*pg/ml Standard Deviation 144000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 26	306000 min*pg/ml Standard Deviation 252000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 39	284000 min*pg/ml Standard Deviation 137000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 52	303000 min*pg/ml Standard Deviation 208000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Day 01	102000 min*pg/ml Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD value is proposed as NA.	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 13	74500 min*pg/ml Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD value is proposed as NA.	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 26	233000 min*pg/ml Standard Deviation 132000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 39	204000 min*pg/ml Standard Deviation 39700	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 52	137000 min*pg/ml Standard Deviation 48900	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Day 01	557000 min*pg/ml Standard Deviation 278000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 13	670000 min*pg/ml Standard Deviation 312000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 26	429000 min*pg/ml Standard Deviation 163000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 39	387000 min*pg/ml Standard Deviation 53800	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 52	768000 min*pg/ml Standard Deviation 391000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Day 01	353000 min*pg/ml Standard Deviation 133000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 13	382000 min*pg/ml Standard Deviation 268000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 26	305000 min*pg/ml Standard Deviation 82100	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 39	575000 min*pg/ml Standard Deviation 455000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 52	622000 min*pg/ml Standard Deviation 455000	—	—	—	—	—

SECONDARY outcome

Timeframe: At Day 01, Week 13, Week 26, Week 39, & Week 52

Population: PK Population

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Day 01	134000 min*pg/ml Standard Deviation 96500	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 13	183000 min*pg/ml Standard Deviation 126000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 26	283000 min*pg/ml Standard Deviation 222000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 39	257000 min*pg/ml Standard Deviation 132000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 52	260000 min*pg/ml Standard Deviation 172000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Day 01	83100 min*pg/ml Standard Deviation 48300	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 13	115000 min*pg/ml Standard Deviation 59300	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 26	197000 min*pg/ml Standard Deviation 121000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 39	166000 min*pg/ml Standard Deviation 81000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 52	125000 min*pg/ml Standard Deviation 76700	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Day 01	525000 min*pg/ml Standard Deviation 251000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 13	642000 min*pg/ml Standard Deviation 353000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 26	408000 min*pg/ml Standard Deviation 148000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 39	365000 min*pg/ml Standard Deviation 44700	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 52	670000 min*pg/ml Standard Deviation 335000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Day 01	312000 min*pg/ml Standard Deviation 119000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 13	342000 min*pg/ml Standard Deviation 245000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 26	300000 min*pg/ml Standard Deviation 79100	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 39	591000 min*pg/ml Standard Deviation 359000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 52	558000 min*pg/ml Standard Deviation 400000	—	—	—	—	—

SECONDARY outcome

Timeframe: At Day 01, Week 13, Week 26, Week 39, & Week 52

Population: PK Population

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Day 01	132000 min*pg/ml Standard Deviation 97300	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 13	182000 min*pg/ml Standard Deviation 127000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 26	282000 min*pg/ml Standard Deviation 222000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 39	256000 min*pg/ml Standard Deviation 132000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 52	258000 min*pg/ml Standard Deviation 169000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Day 01	65900 min*pg/ml Standard Deviation 33600	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 13	112000 min*pg/ml Standard Deviation 62900	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 26	196000 min*pg/ml Standard Deviation 121000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 39	165000 min*pg/ml Standard Deviation 82400	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 52	122000 min*pg/ml Standard Deviation 75700	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Day 01	547000 min*pg/ml Standard Deviation 279000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 13	645000 min*pg/ml Standard Deviation 357000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 26	407000 min*pg/ml Standard Deviation 148000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 39	365000 min*pg/ml Standard Deviation 44300	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 52	672000 min*pg/ml Standard Deviation 334000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Day 01	323000 min*pg/ml Standard Deviation 129000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 13	340000 min*pg/ml Standard Deviation 244000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 26	297000 min*pg/ml Standard Deviation 80700	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 39	567000 min*pg/ml Standard Deviation 361000	—	—	—	—	—
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 52	557000 min*pg/ml Standard Deviation 401000	—	—	—	—	—

SECONDARY outcome

Timeframe: At Day 01, Week 13, Week 26, Week 39, & Week 52

Population: PK Population

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Day 01	4430 pg/ml Standard Deviation 3670	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 13	4350 pg/ml Standard Deviation 1670	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 26	5850 pg/ml Standard Deviation 3260	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 39	5600 pg/ml Standard Deviation 2200	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 52	5640 pg/ml Standard Deviation 2740	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Day 01	2840 pg/ml Standard Deviation 1230	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 13	5970 pg/ml Standard Deviation 2390	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 26	6800 pg/ml Standard Deviation 3360	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 39	4600 pg/ml Standard Deviation 2150	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 52	3870 pg/ml Standard Deviation 2120	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Day 01	14500 pg/ml Standard Deviation 5950	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 13	13400 pg/ml Standard Deviation 6070	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 26	10100 pg/ml Standard Deviation 2970	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 39	6980 pg/ml Standard Deviation 1140	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 52	12900 pg/ml Standard Deviation 6260	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Day 01	13400 pg/ml Standard Deviation 5710	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 13	10500 pg/ml Standard Deviation 6850	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 26	11500 pg/ml Standard Deviation 4290	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 39	18400 pg/ml Standard Deviation 11900	—	—	—	—	—
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 52	13500 pg/ml Standard Deviation 6770	—	—	—	—	—

SECONDARY outcome

Timeframe: At Day 01, Week 13, Week 26, Week 39, & Week 52.

Population: PK Population

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 13	9.43 min Standard Deviation 5.22	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Day 01	13.1 min Standard Deviation 6.33	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 13	14.3 min Standard Deviation 5.5	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 26	16.1 min Standard Deviation 8.69	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 39	17.4 min Standard Deviation 11.9	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 52	16.1 min Standard Deviation 6.27	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Day 01	11.3 min Standard Deviation 6.35	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 13	6 min Standard Deviation 1.41	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 26	10.8 min Standard Deviation 5.5	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 39	15.4 min Standard Deviation 11.6	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 52	14.2 min Standard Deviation 5.76	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Day 01	12.9 min Standard Deviation 9.1	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 13	14 min Standard Deviation 8.42	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 26	12 min Standard Deviation 5.2	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 39	15 min Standard Deviation 0	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 52	14.3 min Standard Deviation 1.53	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Day 01	7.36 min Standard Deviation 3.53	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 26	9 min Standard Deviation 4.69	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 39	11.3 min Standard Deviation 3.59	—	—	—	—	—
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 52	14.5 min Standard Deviation 3.51	—	—	—	—	—

SECONDARY outcome

Timeframe: At Day 01, Week 13, Week 26, Week 39, & Week 52.

Population: PK Population

Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics.

PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞, CL/F, V/F and t1/2 excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected.

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Day 01	134 ml/min/kg Standard Deviation 59.8	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 13	111 ml/min/kg Standard Deviation 58.5	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 26	79.8 ml/min/kg Standard Deviation 48.3	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 39	65.3 ml/min/kg Standard Deviation 32.7	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 52	69 ml/min/kg Standard Deviation 41.2	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Day 1	147 ml/min/kg Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD value is proposed as NA.	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 13	201 ml/min/kg Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD value is proposed as NA.	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 26	79.5 ml/min/kg Standard Deviation 38.4	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 39	75.5 ml/min/kg Standard Deviation 14.8	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 52	122 ml/min/kg Standard Deviation 52.5	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Day 01	65.9 ml/min/kg Standard Deviation 31.6	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 13	58.7 ml/min/kg Standard Deviation 40.4	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 26	79.4 ml/min/kg Standard Deviation 37.7	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 39	78.3 ml/min/kg Standard Deviation 10.9	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 52	49.7 ml/min/kg Standard Deviation 32	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Day 01	95.9 ml/min/kg Standard Deviation 34	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 13	115 ml/min/kg Standard Deviation 78.1	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 26	104 ml/min/kg Standard Deviation 23.2	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 39	73.6 ml/min/kg Standard Deviation 41.6	—	—	—	—	—
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 52	76.5 ml/min/kg Standard Deviation 49.8	—	—	—	—	—

SECONDARY outcome

Timeframe: At Day 01, Week 13, Week 26, Week 39, & Week 52.

Population: PK Population

Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics.

PK parameters for another participant on Day 1 obtained from extrapolation. V/F excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected.

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Day 01	5550 ml/kg Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD value is proposed as NA.	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 13	7810 ml/kg Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD value is proposed as NA.	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 26	3890 ml/kg Standard Deviation 2880	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 39	2250 ml/kg Standard Deviation 284	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 52	3770 ml/kg Standard Deviation 1410	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Day 01	3190 ml/kg Standard Deviation 1790	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 13	2090 ml/kg Standard Deviation 1360	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 26	1960 ml/kg Standard Deviation 829	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 39	2920 ml/kg Standard Deviation 205	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 52	3040 ml/kg Standard Deviation 2630	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Day 01	4070 ml/kg Standard Deviation 2310	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 13	3990 ml/kg Standard Deviation 2960	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 26	3400 ml/kg Standard Deviation 2520	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 39	2330 ml/kg Standard Deviation 1150	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 52	2660 ml/kg Standard Deviation 1420	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Day 01	5240 ml/kg Standard Deviation 1890	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 13	4260 ml/kg Standard Deviation 2960	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 26	2750 ml/kg Standard Deviation 710	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 39	2200 ml/kg Standard Deviation 951	—	—	—	—	—
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 52	2620 ml/kg Standard Deviation 1950	—	—	—	—	—

SECONDARY outcome

Timeframe: At Day 01, Week 13, Week 26, Week 39, & Week 52.

Population: PK Population

Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics.

PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞, CL/F, V/F and t1/2 excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected.

Outcome measures

Measure	Cohort 1: Placebo n=43 Participants Cohort 1 Placebo: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection.	Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day \& 30 µg/kg/day single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9)	Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16) Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8) Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8)	Placebo Placebo: Participants who received placebo single daily subcutaneous injection.	Cohort 3: Placebo Cohort 3 Placebo: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection.	Cohort 3: Vosoritide Cohort 3 Vosoritide: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection.
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Day 01	33.3 min Standard Deviation 8.41	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 13	25.6 min Standard Deviation 3.59	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 26	21 min Standard Deviation 13.1	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 39	26.2 min Standard Deviation 5.46	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 30 μg/kg/day: Week 52	40.1 min Standard Deviation 15.2	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Day 01	41.1 min Standard Deviation 18.8	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 13	26.2 min Standard Deviation 7.1	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 26	19.2 min Standard Deviation 6.14	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 39	22.7 min Standard Deviation 5.36	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 3 30 μg/kg/day: Week 52	24.3 min Standard Deviation 6.58	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Day 01	26.1 min Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD value is proposed as NA.	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 13	26.9 min Standard Deviation NA As the number of subjects assessed in this category is only 1, Standard Deviation (SD) is not applicable. Hence SD value is proposed as NA.	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 26	32.7 min Standard Deviation 9.62	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Day 01	21.7 min Standard Deviation 7.99	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 13	25.4 min Standard Deviation 10.7	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 26	29.2 min Standard Deviation 7.06	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 39	20.9 min Standard Deviation 2.18	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 2 15 μg/kg/day: Week 52	24 min Standard Deviation 12.8	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 39	25.7 min Standard Deviation 7.82	—	—	—	—	—
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 Cohort 1 15 μg/kg/day: Week 52	29 min Standard Deviation 9.12	—	—	—	—	—

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 32 other events

Deaths: 0 deaths

Vosoritide

Serious events: 3 serious events

Other events: 43 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=32 participants at risk Placebo: Participants who received placebo single daily subcutaneous injection.	Vosoritide n=43 participants at risk All Vosoritide : 11 sentinel + 32 randomized participants who received vosoritide 15 µg/kg/day or 30 µg/kg/day, single daily subcutaneous injection.
Investigations Oxygen saturation decreased	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	2.3% 1/43 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Nervous system disorders Petit mal epilepsy	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	0.00% 0/43 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Infections and infestations Gastroenteritis	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	0.00% 0/43 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Psychiatric disorders Autism spectrum disorde	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	0.00% 0/43 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Infections and infestations Pneumonia	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	2.3% 1/43 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Infections and infestations Respiratory syncytial virus bronchiolitis	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	2.3% 1/43 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Infections and infestations Otitis media	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	0.00% 0/43 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Infections and infestations Parainfluenzae virus infection	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	0.00% 0/43 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
General disorders Sudden infant death syndrome	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	2.3% 1/43 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Gastrointestinal disorders Vomiting	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	0.00% 0/43 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Injury, poisoning and procedural complications Skull fracture	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	0.00% 0/43 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Respiratory, thoracic and mediastinal disorders Respiratory distress	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	0.00% 0/43 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.

Other adverse events

Measure	Placebo n=32 participants at risk Placebo: Participants who received placebo single daily subcutaneous injection.	Vosoritide n=43 participants at risk All Vosoritide : 11 sentinel + 32 randomized participants who received vosoritide 15 µg/kg/day or 30 µg/kg/day, single daily subcutaneous injection.
Infections and infestations Rhinitis	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	9.3% 4/43 • Number of events 8 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	7.0% 3/43 • Number of events 3 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Infections and infestations Lower respiratory tract infection	3.1% 1/32 • Number of events 3 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	9.3% 4/43 • Number of events 4 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Infections and infestations Viral infection	12.5% 4/32 • Number of events 8 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	18.6% 8/43 • Number of events 28 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
General disorders Injection site reaction	40.6% 13/32 • Number of events 154 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	79.1% 34/43 • Number of events 3057 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
General disorders Injection site erythema	40.6% 13/32 • Number of events 1738 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	76.7% 33/43 • Number of events 5100 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
General disorders Injection site swelling	6.2% 2/32 • Number of events 3 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	18.6% 8/43 • Number of events 36 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
General disorders Injection site induration	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	11.6% 5/43 • Number of events 14 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
General disorders Injection site urticaria	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	14.0% 6/43 • Number of events 22 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	7.0% 3/43 • Number of events 3 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/32 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	7.0% 3/43 • Number of events 3 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Gastrointestinal disorders Constipation	6.2% 2/32 • Number of events 4 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	11.6% 5/43 • Number of events 7 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Injury, poisoning and procedural complications Fall	9.4% 3/32 • Number of events 5 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	16.3% 7/43 • Number of events 9 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Injury, poisoning and procedural complications Arthropod bite	6.2% 2/32 • Number of events 2 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	14.0% 6/43 • Number of events 7 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.
Skin and subcutaneous tissue disorders Dermatitis diaper	3.1% 1/32 • Number of events 1 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.	9.3% 4/43 • Number of events 5 • Up to Week 56 Safety Follow-Up. The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study. The safety data is presented for the overall vosoritide and placebo cohort. The doses for each of the cohorts were selected such that the exposure to vosoritide, based on pharmacokinetic parameters, was comparable across all 3 cohorts.

Additional Information

Alice Huntsman Labed

BioMarin Pharmaceutical Inc.

Phone: +44 792-756-5104

Email: alice.huntsmanlabed@bmrn.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60