Trial Outcomes & Findings for A Safety, Tolerability, and Efficacy Study of BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease (NCT NCT02678689)

Last Updated: 2025-02-17

Results Overview

Rate of decline in 0 to 6-point ML score, \& primary analysis was based on up to 3-1 matching of Study 190-901 evaluable participants with Study 190-203 ITT participants. Rate of decline =(-1)x(48x7)x(Ending score - Starting score)/(Ending date - Starting date) A positive rate of decline means that subject declined, a negative rate of decline means that subject improved. The combined motor/gait and language (ML) score, as derived from Hamburg CLN2 rating scale, immediately preceding first infusion. The combined ML score is determined as sum of 0-3 point motor(M) \& language(L) subscales where 0 represents no function, \& 3 represents normal function, \& can range from 0(severely impaired) to 6(normal). Thus,high scores describe better function \& low scores describe poor function. The starting assessment is baseline ML assessment \& ending assessment is last ML score \>0. Note for Study 190-901, baseline ML assessment is defined as assessment of matching to Study 190-203 subj.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Baseline to Last assessment (Week 169)

Results posted on

2025-02-17

Participant Flow

Study 190-203 was conducted at 4 clinic sites:One each in Germany, Italy, the United Kingdom and the United States. The comparator group for determination of the primary efficacy outcome measures in this study was comprised of 29 Natural History (NH) subjects with late-infantile neuronal ceroid lipofuscinosis disease, also known as classical late-infantile CLN2, cLINCL, or Jansky-Bielschowsky disease, a form of Batten Disease (CLN2) disease selected from the DEM-CHILD database (NCT04613089).

A total of 14 participants were enrolled and treated in study 190-203. 13 participants completed the study, and 1 participant withdrew to receive treatment commercially. The 190-203 study required enrollment of at least 10 participants, including at least 5 participants with a combined ML score \>= 5 points (mild or pre-symptomatic disease), at least 5 participants with a ML score \< 5points (moderate disease), and at least 5 participants \< 2 years of age.

Participant milestones

Participant milestones
Measure	BMN 190-203 BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Overall Study STARTED	14	29
Overall Study COMPLETED	13	29
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	BMN 190-203 BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Overall Study Participant chose to receive commercial drug in their home country	1	0

Baseline Characteristics

One subject in the natural history group had missing baseline values for the vision and seizure domains. Therefore MLVS score could not be calculated.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator:190-901 Participants n=29 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart	Total n=41 Participants Total of all reporting groups
Age, Continuous	2.7 years STANDARD_DEVIATION 1.12 • n=12 Participants	2.7 years STANDARD_DEVIATION 1.09 • n=29 Participants	2.7 years STANDARD_DEVIATION 1.09 • n=41 Participants
Sex/Gender, Customized Female	8 Participants n=12 Participants	15 Participants n=29 Participants	23 Participants n=41 Participants
Sex/Gender, Customized Male	4 Participants n=12 Participants	14 Participants n=29 Participants	18 Participants n=41 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=12 Participants	0 Participants n=29 Participants	1 Participants n=41 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=12 Participants	0 Participants n=29 Participants	11 Participants n=41 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants	29 Participants n=29 Participants	29 Participants n=41 Participants
Race/Ethnicity, Customized White	12 Participants n=12 Participants	0 Participants n=29 Participants	12 Participants n=41 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=12 Participants	29 Participants n=29 Participants	29 Participants n=41 Participants
CLN2 motor-language (ML) score	5.0 score on a scale STANDARD_DEVIATION 1.41 • n=12 Participants	5.0 score on a scale STANDARD_DEVIATION 1.38 • n=29 Participants	5.0 score on a scale STANDARD_DEVIATION 1.37 • n=41 Participants
CLN2 motor scale score at Baseline	2.4 score on a scale STANDARD_DEVIATION 0.79 • n=12 Participants	2.6 score on a scale STANDARD_DEVIATION 0.54 • n=29 Participants	2.6 score on a scale STANDARD_DEVIATION 0.63 • n=41 Participants
CLN2 language scale score at Baseline	2.6 Score on a scale STANDARD_DEVIATION 0.67 • n=12 Participants	2.4 Score on a scale STANDARD_DEVIATION 0.93 • n=29 Participants	2.4 Score on a scale STANDARD_DEVIATION 0.86 • n=41 Participants
CLN2 motor-language-vision-seizure (MLVS) score	10.9 Score on a scale STANDARD_DEVIATION 1.56 • n=12 Participants • One subject in the natural history group had missing baseline values for the vision and seizure domains. Therefore MLVS score could not be calculated.	10.2 Score on a scale STANDARD_DEVIATION 2.70 • n=28 Participants • One subject in the natural history group had missing baseline values for the vision and seizure domains. Therefore MLVS score could not be calculated.	10.4 Score on a scale STANDARD_DEVIATION 2.42 • n=40 Participants • One subject in the natural history group had missing baseline values for the vision and seizure domains. Therefore MLVS score could not be calculated.
Age at disease onset (years)	2.1 years STANDARD_DEVIATION 0.82 • n=5 Participants • Age at disease onset was missing for several subjects in both 190-203 and the natural history comparator.	2.6 years STANDARD_DEVIATION 0.82 • n=11 Participants • Age at disease onset was missing for several subjects in both 190-203 and the natural history comparator.	2.5 years STANDARD_DEVIATION 0.83 • n=16 Participants • Age at disease onset was missing for several subjects in both 190-203 and the natural history comparator.

PRIMARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Matched ITT BMN 190-203: Two subjects in 190-203 ITT population (N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: • Equal ML score • Age within 3 months • Genome: equal number of common alleles (c.622C→T, c.509.1G→C) Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=29 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Motor Language (ML) Scale: Rate of Decline in the 0 to 6-point ML Score.	0.15 change in score/48 wk Standard Deviation 0.243	1.30 change in score/48 wk Standard Deviation 0.857

PRIMARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Matched ITT BMN 190-203: Two subjects in 190-203 ITT Population(N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: Equal ML score, age within 3 months and genome with equal number of common alleles(c.622C→T, c.509.1G→C). Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description.

An unreversed 2-point decline is any decline of 2 points or more that had not reversed to a 1-point decline (or better) at last recorded observation. An unreversed score of 0 is a decline to 0 that had not increased to a score \>0 at last recorded observation ML score decline is measured by motor \& language domains on CLN2 rating scale. Combined motor/gait \&language (ML) score, as derived from Hamburg CLN2 rating scale, immediately preceding first infusion. Combined ML score is determined as sum of the 0-3 point motor(M)\&language(L) where 0 represents no function, \& 3 represents normal function, \& can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function \& low scores describe poor function Model includes data up to week 169. Estimates from the model are presented for Wks 49, 97 \& 145 No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had unreversed 2-point decline/score of 0 at given time points.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=29 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Probability of Unreversed 2-Point Decline in Motor-language (ML) Score or Score of 0 Probability of decline: Week 49	0.0 Probability of decline Interval 0.0 to 0.0	0.141 Probability of decline Interval 0.05 to 0.35
Probability of Unreversed 2-Point Decline in Motor-language (ML) Score or Score of 0 Probability of decline: Week 97	0.083 Probability of decline Interval 0.01 to 0.46	0.397 Probability of decline Interval 0.23 to 0.62
Probability of Unreversed 2-Point Decline in Motor-language (ML) Score or Score of 0 Probability of decline: Week 145	0.167 Probability of decline Interval 0.04 to 0.52	0.774 Probability of decline Interval 0.59 to 0.92

PRIMARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Matched ITT BMN 190-203: Two subjects in 190-203 ITT Population (N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: Equal ML score, age within 3 months and genome with equal number of common alleles (c.622C→T, c.509.1G→C). Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description

The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first infusion. The combined ML score is determined as the sum of the 0-3 point motor (M) and language (L) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function and low scores describe poor function. Model includes data up to week 169. Estimates from the model are presented for Weeks 49, 97 and 145. No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had unreversed decline/score of 0 at given time points

Outcome measures

Outcome measures
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=29 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Probability of Decline of Unreversed Motor-language (ML) Score of 0 Probability of decline: Week 49	0.0 Probability of decline Interval 0.0 to 0.0	0.03 Probability of decline Interval 0.0 to 0.26
Probability of Decline of Unreversed Motor-language (ML) Score of 0 Probability of decline: Week 97	0.0 Probability of decline Interval 0.0 to 0.0	0.149 Probability of decline Interval 0.06 to 0.37
Probability of Decline of Unreversed Motor-language (ML) Score of 0 Probability of decline: Week 145	0.0 Probability of decline Interval 0.0 to 0.0	0.336 Probability of decline Interval 0.18 to 0.57

PRIMARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Matched ITT BMN 190-203: Two subjects in 190-203 ITT Population (N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: Equal ML score, age within 3 months and genome with equal number of common alleles (c.622C→T, c.509.1G→C). Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description.

Rate of decline = (-1) x (48 x 7) x (Ending score - Starting score)/(Ending date - Starting date). A positive rate of decline means that the subject declined, a negative rate of decline means that the subject improved. The 0-3 point motor (M) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, and 3 represents normal function. Thus, high scores describe better function, and low scores describe poor function.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=29 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Rate of Decline in Individual Motor Domains	0.05 change in score/48 wk Standard Deviation 0.120	0.59 change in score/48 wk Standard Deviation 0.496

PRIMARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Matched ITT BMN 190-203: Two subjects in 190-203 ITT Population (N=14) were excluded from the 190-203 ITT analysis with matching (N=12) who did not match with any 190-901 subjects on the matching criteria. The matching criteria at baseline were: Equal ML score, age within 3 months and genome with equal number of common alleles (c.622C→T, c.509.1G→C). Matched 190-901 Natural history population: 29 subjects from DEM-CHILD database satisfying the criteria listed in the Arm/Group description.

Rate of decline = (-1) x (48 x 7) x (Ending score - Starting score)/(Ending date - Starting date). A positive rate of decline means that the subject declined, a negative rate of decline means that the subject improved. The 0-3 point language (L) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, and 3 represents normal function. Thus, high scores describe better function and low scores describe poor function. Patients with baseline score of 0 are excluded.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=28 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Rate of Decline in Individual Language Domains	0.10 change in score/48 wk Standard Deviation 0.146	0.77 change in score/48 wk Standard Deviation 0.715

SECONDARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Matched ITT BMN190-203:2 subj in190-203 ITT Population(N=14)were excluded from 190-203 ITT analysis with matching(N=12)who did not match with any190-901 subj on matching criteria.Matching criteria at baseline were:Equal ML score,age\<3 months\&genome with equal no.of common alleles(c.622C→T,c.509.1G→C). Matched190-901 Natural history population:29 subj from DEM-CHILD database satisfying criteria listed in Arm descp Model includes data upto wk169.Estimates from model are presented for Wks 49\&97

Disease manifestation is defined as post-baseline consecutive measurements of M,L,V/S scores\<3, measured atleast 22days apart. Combined motor-language-vision-seizure(MLVS)score as derived from Hamburg CLN2 rating scale, is determined as sum of 0-3 point motor(M)language(L)visio(V)\&seizure(S) subscales where 0 represents no function,\&3 represents normal function,\&can range from 0(severely impaired)to12(normal).Thus, high scores describe better function \& low scores describe poor function. 901 subj weighted according to no.of matches:weights for 3,2,\&1 study 901 subj matched to a given study 203 subj are 1/3,1/2, \&1 times N901/N203 respectively. N901 is no.of 901 subj matched to 203 subj(ie.18)\&N203 is no.203 subj who had matches (i.e.7).203 subj who had matches were assigned weight of 1. No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had decline of disease manifestation at given time points

Outcome measures

Outcome measures
Measure	BMN 190-203 n=7 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=18 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Probability of Decline of Disease Manifestation at Week 49 & 97 Probability of decline: Week 49	0.143 Probability of decline Interval 0.02 to 0.67	0.405 Probability of decline Interval 0.22 to 0.67
Probability of Decline of Disease Manifestation at Week 49 & 97 Probability of decline: Week 97	0.286 Probability of decline Interval 0.08 to 0.74	0.762 Probability of decline Interval 0.55 to 0.93

SECONDARY outcome

Timeframe: Baseline to Week 145

Population: Matched ITT BMN190-203:2 subj in 190-203 ITT Pop(N=14) were excluded from 190-203 ITT analysis with matching(N=12) who did not match with any 190-901 subj on matching criteria. Matching criteria at baseline were:Equal ML score, age within 3 months \& genome with equal no. of common alleles(c.622C→T, c.509.1G→C). Matched 190-901 Natural history pop:29 subj from DEM-CHILD database satisfying criteria listed in Arm/Group descp. No.of subj analyzed for 190-901=0 \& hence this arm is not included

Disease manifestation is defined as post-baseline consecutive measurements of M,L,V/S scores\<3,measured atleast 22days apart Combined MLVS score,as derived from Hamburg CLN2 rating scale,is determined as sum of 0-3 point motor(M)language(L)vision(V)\&seizure(S) subscales where 0 represents no function,\&3 represents normal function,\&can range from 0(severely impaired) to 12(normal).Thus,high scores describe better function\&low scores describe poor function 901 subj weighted according to no.of matches:weights for 3,2,\&1 study 901 subj matched to given study 203 subj are 1/3,1/2, \&1 times N901/N203 respectively.N901 is no.of 901 subj matched to 203 subj(ie.18)\&N203 is no.203 subj who had matches(i.e.7).203 subj who had matches were assigned weight of 1 Model includes data upto wk169.Estimates from model are presented for Wk145 No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had decline of disease manifestation at given time point

Outcome measures

Outcome measures
Measure	BMN 190-203 n=4 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Probability of Decline of Disease Manifestation at Week 145	0.429 Probability of decline Interval 0.16 to 0.83	—

SECONDARY outcome

Timeframe: Baseline to Week 49, Week 97, Week 145, & Week 169

Population: 190-901 participants weighted according to no. of matches: weights for 3,2,\&1 study 190-901 participant matched to a given Study190-203 participant were1/3,1/2,\&1 times N901/N203, respectively. N901 was no. of 190-901 participants matched to 190-203 participants (ie,29) \&N203 was no. of 190-203 participants who had matches (ie,12).190-203 participants who had matches were assigned weight of 1. Each participant in Study 190-901 had their scores imputed to time points using linear interpolation

The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first infusion. The combined ML score is determined as the sum of the 0-3 point motor (M) and language (L) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=29 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Change From Baseline in ML Scale Score Change from Baseline to Week 49	-0.0 score on a scale Standard Deviation 0.57	-0.8 score on a scale Standard Deviation 1.05
Change From Baseline in ML Scale Score Change from Baseline to Week 97	0.0 score on a scale Standard Deviation 0.43	-1.6 score on a scale Standard Deviation 1.22
Change From Baseline in ML Scale Score Change from Baseline to Week 145	-0.4 score on a scale Standard Deviation 0.78	-3.1 score on a scale Standard Deviation 1.61
Change From Baseline in ML Scale Score Change from Baseline to Week 169	-0.4 score on a scale Standard Deviation 0.67	-3.7 score on a scale Standard Deviation 2.39

SECONDARY outcome

Timeframe: Baseline to Week 49, Week 97, Week 145, & Week 169

The combined motor-language-vision (MLV) score, as derived from the Hamburg CLN2 rating scale, is determined as the sum of the 0-3 point motor (M), language (L) \& vision (V) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 9 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=29 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Changes From Baseline in MLV Scale Score Change from Baseline to Week 145	-0.7 score on a scale Standard Deviation 1.06	-3.9 score on a scale Standard Deviation 1.98
Changes From Baseline in MLV Scale Score Change from Baseline to Week 49	-0.1 score on a scale Standard Deviation 0.74	-1.0 score on a scale Standard Deviation 1.31
Changes From Baseline in MLV Scale Score Change from Baseline to Week 97	-0.1 score on a scale Standard Deviation 0.51	-2.1 score on a scale Standard Deviation 1.71
Changes From Baseline in MLV Scale Score Change from Baseline to Week 169	-0.7 score on a scale Standard Deviation 1.10	-4.5 score on a scale Standard Deviation 3.04

SECONDARY outcome

Timeframe: Baseline to Week 49, Week 97, Week 145, & Week 169

The combined motor-language-vision-seizure (MLVS) score, as derived from the Hamburg CLN2 rating scale, is determined as the sum of the 0-3 point motor (M) and language (L) vision (V) and seizure (S) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 12 (normal). Thus, high scores describe better function and low scores describe poor function. Some participants did not have follow-up at all time points.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=12 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants n=29 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score. Change from Baseline to Week 49	-0.2 score on a scale Standard Deviation 0.86	-1.5 score on a scale Standard Deviation 1.39
Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score. Change from Baseline to Week 97	-0.1 score on a scale Standard Deviation 0.51	-3.0 score on a scale Standard Deviation 1.78
Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score. Change from Baseline to Week 145	-0.6 score on a scale Standard Deviation 0.99	-5.5 score on a scale Standard Deviation 2.48
Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score. Change from Baseline to Week 169	-0.6 score on a scale Standard Deviation 1.03	-6.4 score on a scale Standard Deviation 3.43

SECONDARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Intent-to-treat (ITT) population. One subject did not have any follow-up MRI data available.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=13 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Percentage Change From Baseline to Last Assessment: Volume of Cerebrospinal Fluid (mL)	0.7 Percentage Standard Deviation 13.18	—

SECONDARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Intent-to-treat (ITT) population. One subject did not have any follow-up MRI data available.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=13 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Percentage Change From Baseline to Last Assessment: Volume of Total Cortical Gray Matter (mL)	-10.3 Percentage Standard Deviation 13.86	—

SECONDARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Intent-to-treat (ITT) population. One subject did not have any follow-up MRI data available.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=13 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Percentage Change From Baseline to Last Assessment: Volume of Total White Matter (mL)	5.4 Percentage Standard Deviation 20.86	—

SECONDARY outcome

Timeframe: Baseline to Last assessment (Week 169)

Population: Intent-to-treat (ITT) population. One subject did not have any follow-up MRI data available.

The apparent diffusion coefficient (ADC) represents the calculated diffusion coefficient of water molecules in the direction of the applied gradients measured during diffusion MRI, a technique used to explore the architecture and microstructural properties of both the white and gray matter of the brain.

Outcome measures

Outcome measures
Measure	BMN 190-203 n=13 Participants BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.	Natural History Comparator: 190-901 Participants The NH comparator population consisted of subjects from the DEM-CHILD database who satisfied the 190-203 inclusion criteria. The Study 190-901 evaluable population was required to have: * At least one assessment ML \>= 3 * At least two ML assessments in the range 1 - 6 and at least 6 months apart
Change From Baseline to Last Assessment: Whole Brain Apparent Diffusion Coefficient Value	0.0 mm^2/s Standard Deviation 0.04	—

Adverse Events

BMN 190 Recombinant Human Tripeptidyl Peptidase-1 (rhTPP1)

Serious events: 12 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BMN 190 Recombinant Human Tripeptidyl Peptidase-1 (rhTPP1) n=14 participants at risk BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.
Ear and labyrinth disorders Deafness unilateral	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Pyrexia	28.6% 4/14 • Number of events 7 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Escherichia urinary tract infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Mycoplasma infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Pneumonia	7.1% 1/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Pyelonephritis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Dental caries	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Gastrointestinal fistula	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Immune system disorders Hypersensitivity	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Immune system disorders Anaphylactic reaction	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Status epilepticus	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Complication of device insertion	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Medical device site haematoma	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Medical device site irritation	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Influenza	14.3% 2/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Corona virus infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Rhinitis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Rhinovirus infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Upper respiratory tract infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Viral infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Dysphagia	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Pleocytosis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Periorbital haematoma	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Propionibacterium test positive	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Product Issues Device leakage	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Hypoxia	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)

Other adverse events

Other adverse events
Measure	BMN 190 Recombinant Human Tripeptidyl Peptidase-1 (rhTPP1) n=14 participants at risk BMN 190 was administered by continuous Intracerebroventricular (ICV) infusion at the rate of 2.5 mL/hour for approximately 4 hours every 14 (+/-3) days, preferably in the morning. The recommended dose of BMN 190 is according to the participant's age: Birth to \< 6 months: 100 mg, 6 months to \< 1 year: 150 mg, 1 year to \< 2 years: 200 mg (first four doses), 300 mg (subsequent doses) \>=2 years: 300 mg. The treatment continued for the duration of at least 144 weeks or until all procedures were completed or the participant discontinued from the study. BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Intracerebroventricular access device: Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.
General disorders Pyrexia	85.7% 12/14 • Number of events 62 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Upper respiratory tract infection	85.7% 12/14 • Number of events 26 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Extensor plantar response	50.0% 7/14 • Number of events 7 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Gastroenteritis	50.0% 7/14 • Number of events 10 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Generalised tonic-clonic seizure	42.9% 6/14 • Number of events 18 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Vomiting	35.7% 5/14 • Number of events 7 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Contusion	28.6% 4/14 • Number of events 8 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Cough	28.6% 4/14 • Number of events 9 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Dysphagia	28.6% 4/14 • Number of events 5 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Immune system disorders Hypersensitivity	28.6% 4/14 • Number of events 20 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Influenza	28.6% 4/14 • Number of events 6 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Medication monitoring error	28.6% 4/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Atonic seizures	21.4% 3/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Constipation	21.4% 3/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Corona virus infection	21.4% 3/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Product Issues Device leakage	21.4% 3/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Dystonia	21.4% 3/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Partial seizures	21.4% 3/14 • Number of events 28 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Skin and subcutaneous tissue disorders Rash	21.4% 3/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Rhinitis	21.4% 3/14 • Number of events 5 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Seizure	21.4% 3/14 • Number of events 8 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Speech disorder developmental	21.4% 3/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Viral upper respiratory tract infection	21.4% 3/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Abdominal pain	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Bronchitis	14.3% 2/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Dental caries	14.3% 2/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Diarrhoea	14.3% 2/14 • Number of events 5 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Dyskinesia	14.3% 2/14 • Number of events 34 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Epilepsy	14.3% 2/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Epistaxis	14.3% 2/14 • Number of events 8 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Foreign body	14.3% 2/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Psychiatric disorders Insomnia	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 2/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Product Issues Needle issue	14.3% 2/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Otitis media	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Parainfluenzae virus infection	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Skin abrasion	14.3% 2/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Psychiatric disorders Sleep disorder	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Stomatitis	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Tonsillitis	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Tremor	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Viral test positive	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Eye disorders Visual impairment	14.3% 2/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Immune system disorders Anaphylactic reaction	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Aphthous ulcer	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Asthenia	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Athetosis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Cardiac disorders Atrioventricular block second degree	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Psychiatric disorders Attention deficit/hyperactivity disorder	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Congenital, familial and genetic disorders Bicuspid aortic valve	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Body temperature increased	7.1% 1/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations CSF red blood cell count positive	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Chills	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Complication of device insertion	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Ear and labyrinth disorders Deafness unilateral	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Skin and subcutaneous tissue disorders Dermatitis atopic	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Product Issues Device breakage	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Product Issues Device malfunction	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Immune system disorders Drug hypersensitivity	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Eye disorders Dry eye	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Ear and labyrinth disorders Ear haemorrhage	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Ear infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Skin and subcutaneous tissue disorders Eczema	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Electrocardiogram abnormal	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Electroencephalogram abnormal	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Skin and subcutaneous tissue disorders Erythema	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Escherichia urinary tract infection	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Exanthema subitum	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Eye disorders Eye movement disorder	7.1% 1/14 • Number of events 11 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Eyelid contusion	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Fall	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Febrile convulsion	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Foot fracture	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Fungal skin infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Gait disturbance	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Gastrointestinal fistula	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Gastrooesophageal reflux disease	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Vascular disorders Haematoma	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Renal and urinary disorders Haematuria	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Head injury	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Headache	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Hepatic enzyme increased	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Hordeolum	7.1% 1/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Human rhinovirus test positive	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Metabolism and nutrition disorders Hypernatraemia	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Vascular disorders Hypertension	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Hypoxia	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Psychiatric disorders Irritability	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Laceration	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Language disorder	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Laryngitis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Malaise	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Medical device site haematoma	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Medical device site irritation	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Medical device site swelling	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Mycoplasma infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Myoclonic epilepsy	7.1% 1/14 • Number of events 4 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Otitis externa	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
General disorders Pain	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Musculoskeletal and connective tissue disorders Pain in jaw	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Paronychia	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Partial seizures with secondary generalisation	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Periorbital haematoma	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Periorbital haemorrhage	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Petit mal epilepsy	7.1% 1/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Pharyngitis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Pharyngotonsillitis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Pleocytosis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Pneumonia	7.1% 1/14 • Number of events 3 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Pneumonia chlamydial	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Injury, poisoning and procedural complications Procedural pain	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Propionibacterium test positive	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Pyelonephritis	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Pyuria	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Skin and subcutaneous tissue disorders Rash generalised	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Skin and subcutaneous tissue disorders Rash macular	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Respiratory disorder	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Respiratory syncytial virus infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Respiratory syncytial virus test	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Respiratory tract infection viral	7.1% 1/14 • Number of events 2 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Investigations Respirovirus test positive	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Rhinovirus infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Rotavirus infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Immune system disorders Seasonal allergy	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Seizure cluster	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Nervous system disorders Status epilepticus	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Respiratory, thoracic and mediastinal disorders Stridor	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Congenital, familial and genetic disorders Talipes	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Gastrointestinal disorders Toothache	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Renal and urinary disorders Urinary retention	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Urinary tract infection bacterial	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Reproductive system and breast disorders Vaginal discharge	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)
Infections and infestations Viral infection	7.1% 1/14 • Number of events 1 • Up-to Safety Follow-Up (6 months after last dose). Atrioventricular block 2nddegree was assessed non-serious by inv but was later upgraded to serious by BioMarin.Inv assessed event as not related to BMN190;however,due to absence of alternative etiological factors\&strong temporal relationship,BioMarin conservatively assessed event possibly related to BMN190.This event was considered a suspected unexpected serious adverse reaction(SUSAR) AEs\&death were collected for BMN190-203 study but it was not collected for BMN190-901(Natural History study)

Additional Information

Pascal Reisewitz, Global Medical Director, PhD

BioMarin Pharmaceutical Inc

Phone: 1-800-983-4587

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restrictions on the PI are that (i) they cannot publish results communications until after the multicenter dataset is published, (ii) the sponsor has an opportunity to review results communications prior to public release, and (iii) the sponsor can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days.
Publication restrictions are in place

Restriction type: OTHER