Trial Outcomes & Findings for A Long-Term Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency (NCT NCT02004704)

Results Overview

An AE: Any untoward medical occurrence in participant or clinical investigation participant administered with pharmaceutical product, which did not necessarily have to have causal relationship with study treatment. SAEs: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, was medically important event. TEAEs: AEs that started during on-treatment period-either in this study or in original study which were ongoing at the time the participant signed the written informed consent. An AESI: AE (serious or nonserious) of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor was appropriate.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Results posted on

2024-07-03

Participant Flow

The study was conducted at 9 investigational sites in 6 countries between 04 Dec 2013 and 06 Sep 2023.

A total of 25 participants (5 adult participants from study DFI13412 \[NCT01722526\] and 20 pediatric participants from study DFI13803 \[NCT02292654\]) directly rolled over and continued treatment in this study.

Participant milestones

Participant milestones
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 milligram/kilogram \[mg/kg\]) via intravenous (IV) infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Overall Study STARTED	5	20
Overall Study COMPLETED	5	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Long-Term Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.	Total n=25 Participants Total of all reporting groups
Age, Continuous	32.0 years STANDARD_DEVIATION 9.25 • n=5 Participants	7.6 years STANDARD_DEVIATION 4.43 • n=7 Participants	12.5 years STANDARD_DEVIATION 11.36 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants	17 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Southeast Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

An AE: Any untoward medical occurrence in participant or clinical investigation participant administered with pharmaceutical product, which did not necessarily have to have causal relationship with study treatment. SAEs: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, was medically important event. TEAEs: AEs that started during on-treatment period-either in this study or in original study which were ongoing at the time the participant signed the written informed consent. An AESI: AE (serious or nonserious) of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor was appropriate.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) Except Infusion-Associated Reactions (IARs) Any TEAEs leading to death	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) Except Infusion-Associated Reactions (IARs) Any TEAE	5 Participants	20 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) Except Infusion-Associated Reactions (IARs) Any TESAE	1 Participants	10 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) Except Infusion-Associated Reactions (IARs) AESI: Any Pregnancies	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) Except Infusion-Associated Reactions (IARs) AESI: Symptomatic Overdose	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) Except Infusion-Associated Reactions (IARs) AESI: Dose-limiting toxicities	0 Participants	10 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) Except Infusion-Associated Reactions (IARs) Any TEAEs leading to treatment discontinuation	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

Protocol-defined IARs were AEs that occurred during the infusion or within up to 24 hours after the start of infusion and were considered as related or possibly related to the study treatment by the investigator or the sponsor. Events occurring greater than or equal to (\>=) 24 hours after the start of an infusion might have been judged an IAR at the discretion of the investigator or sponsor. Algorithm-defined IARs were all AEs that started between the start of infusion and the end of infusion plus 24 hours, irrespective of the perceived relation with study treatment.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Number of Participants With IARs Protocol-defined IARs	4 Participants	13 Participants
Number of Participants With IARs Algorithm-defined IARs	5 Participants	20 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study), Month 78

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

A complete physical examination included assessment of the participant's general appearance, general neurological status, skin, head, eyes, ears, nose, throat, lymph nodes, heart, lungs, abdomen, and extremities/joints. Shift from Baseline was monitored. An abbreviated physical exam (general appearance only) was only performed pre- and post-infusion for those who did not do complete exam.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Lungs	0 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Abdomen	1 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Extremities/Joints	0 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Abbreviated Physical Exam	0 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam General Appearance	0 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam General Neurological Status	0 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Skin	1 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Head, Eyes, Ears, Nose and Throat	1 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Lymph Nodes	0 Participants	—
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Heart	0 Participants	—

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study), Month 84

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

A complete physical examination included assessment of the participant's general appearance, skin, head, eyes, ears, nose, throat, lymph nodes, heart, lungs, abdomen, and extremities/joints. Shift from Baseline was monitored. An abbreviated physical exam (general appearance only) was only performed pre- and post-infusion for those who did not do complete exam.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Abbreviated Physical Exam	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Extremities/Joints	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam General Appearance	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Skin	1 Participants	—
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Head, Eyes, Ears, Nose and Throat	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Lymph Nodes	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Heart	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Lungs	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam Abdomen	2 Participants	—

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study), Month 78

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Extended neurological examination for adults included examination of mental status. Shift from Baseline was monitored.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
For Adults: Number of Participants With Abnormality in Extended Neurological Examinations	0 Participants	—

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study), Month 84

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

The neurological examination in pediatric participants included examination of mental status, cranial nerve examination, motor examination: tone, reflexes examination, sensory examination, coordination, gait and coordination, and strength examination. Shift from Baseline was monitored.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations Mental Status	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations Cranial Nerve Examination	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations Motor Examination: Tone	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations Reflexes Examination	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations Sensory Examination	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations Coordination	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations Gait and Coordination	0 Participants	—
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations Strength Examination	0 Participants	—

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

PCSA: Heart Rate: High: \>=120 beats per minute (bpm) (adults \[ad\], adolescents \[ado\], children \[chi\]), \>=140 bpm (early chi \[ec\]), \>=175 bpm (infants\[inf\]) \& increase from baseline (IFB)\>=20 bpm for all age ranges (AAR), HR Low: \<=50 bpm (ad, ado, chi), \<=75 bpm (ec), \<=80 bpm (inf) \& decrease from baseline (DFB) \>=20 bpm for AAR. Systolic blood pressure: High: \>= 160 millimeters of mercury (mmHg) (ad); \>=119 mmHg (ado), \>=108 mmHg (chi), \>=101 mmHg (ec),\>=98 mmHg (inf) \& IFB \>=20 mmHg for AAR. SBP Low: \<=95 mmHg (ad), \<=90 mmHg (ado), \<= 80mm Hg (chi), \<=70 mmHg (ec), \<=70 mmHg (inf) \& DFB \>=20 mmHg for AAR. Diastolic blood pressure: High:\>110 mmHg (ad), \>=78 mmHg (ado), \>=72 mmHg (chi), \>=59 mmHg (ec), \>=54 mmHg (inf) and IFB \>=10 mmHg for AAR. DBP Low:\<=45 mmHg (ad), \<=54 mmHg (ado), \<=48 mmHg (chi), \<=34mmHg (ec and inf) \& DFB\>=10 mmHg for AAR.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Heart Rate: Low	2 Participants	10 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Systolic blood pressure: High	2 Participants	16 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Systolic blood pressure: Low	5 Participants	11 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Diastolic blood pressure: High	0 Participants	19 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Diastolic blood pressure: Low	5 Participants	19 Participants
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Heart Rate: High	1 Participants	9 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

PCSA: Creatinine High, category 1: \>=150 micromole/L (umol) (adults), \>=132 umol/L or 1.5 mg/deciliter (dL) (adolescents), \>=90 umol/litre (L) or 1.1 mg/dL (children), \>53 umol/L or 0.6 mg/dL (early children and infants); category 2: \>=30% IFB (adults). Blood Urea Nitrogen: \>=17 millimole (mmol)/L (adults), \>=6.4 mmol/L or 18 mg/dL (pediatrics \[ped\]). Glucose Low\<=3.9 mmol/L and \<lower limit of normal (adults), \<2.7 mmol/L (ped), High: \>=11.1 mmol/L (unfasted), \>7 mmol/L (fasted) (adults), \>=7 mmol/L (fasted after \>12 hours of fast); \>=10.0 mmol/L (unfasted) (ped).

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Number of Participants With PCSA in Clinical Chemistry Parameters Creatinine: High, category 1	0 Participants	0 Participants
Number of Participants With PCSA in Clinical Chemistry Parameters Creatinine: High, category 2	1 Participants	4 Participants
Number of Participants With PCSA in Clinical Chemistry Parameters Blood Urea Nitrogen: High	0 Participants	15 Participants
Number of Participants With PCSA in Clinical Chemistry Parameters Glucose: Low	5 Participants	2 Participants
Number of Participants With PCSA in Clinical Chemistry Parameters Glucose: High	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

PCSA: Alanine aminotransferase (ALT) \>3 x upper limit of normal (ULN). Aspartate aminotransferase (AST) \>3 x ULN. Alkaline phosphatase (ALP) \> 1.5 x ULN. Total Bilirubin \>1.5 x ULN (ad) and \>1.3 x ULN (ped). ALT and total bilirubin: ALT \> 3 x ULN and total bilirubin \> 2 x ULN.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Number of Participants With PCSA in Liver Function Tests ALT	0 Participants	5 Participants
Number of Participants With PCSA in Liver Function Tests AST	0 Participants	6 Participants
Number of Participants With PCSA in Liver Function Tests ALP	0 Participants	5 Participants
Number of Participants With PCSA in Liver Function Tests Total Bilirubin	3 Participants	1 Participants
Number of Participants With PCSA in Liver Function Tests ALT and Total Bilirubin	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

PCSA: White blood cells (WBC): Low: \<3.0 Giga (G)/L (Non-Black \[NB\])/\<2.0 G/L (Black \[B\])(ad), \<4.5 G/L (ado), \<5.0 G/L(chi), \<3.0 G/L (ec), \<4.0 G/L (inf), High: \>=16.0 G/L(ad), \>13.5 G/L (ado), \>17.0 G/L(chi), \>16 G/L (ec), \>20 G/L (inf). Hemoglobin-ad: Low-1: \<=115 g/dL (Male \[M\])/\<=95 g/dL (Female \[F\]), 20% DFB for both, High:\>=185 g/L (M)/\>=165 g/L (F), Low-2: DFB\>=20 g/L (ad), \<10 g/dL (ado, chi, ec); \<9.0 g/dL (inf); 20% DFB for all. Platelets: Low: \<100 G/L (AAR) and 20% DFB and High: \>=700 G/L (ad and ped).

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Number of Participants With PCSA in Hematology Parameters WBC: Low	2 Participants	16 Participants
Number of Participants With PCSA in Hematology Parameters WBC: High	0 Participants	0 Participants
Number of Participants With PCSA in Hematology Parameters Hemoglobin: Low-1	0 Participants	0 Participants
Number of Participants With PCSA in Hematology Parameters Hemoglobin: High	1 Participants	0 Participants
Number of Participants With PCSA in Hematology Parameters Hemoglobin: Low-2	2 Participants	0 Participants
Number of Participants With PCSA in Hematology Parameters Platelets: Low	2 Participants	7 Participants
Number of Participants With PCSA in Hematology Parameters Platelets: High	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

PCSA: Heart rate: High:\>=120 bpm (ad, ado, chi), \>=140 bpm (ec), \>=175 bpm (inf) \& IFB\>=20 bpm for AAR, Heart rate: Low: \<=50 bpm (ad, ado, chi), \<=75 bpm (ec), \<=80 bpm (inf) \& DFB \>=20 bpm for AAR. PR duration: High: \>=200 milliseconds (ms) (ad) and IFB\>=20 ms, \>180 ms (ado), 170 ms (chi), 160 ms (ec), and 140 ms (inf). QT correction-Bazett (QTcB): Borderline absolute (category 1): 431-450 ms (ad and ado M, chi, ec and inf), 451-470 ms (ad and ado F), Prolonged-absolute (category 2): \>450 ms (ad and ado M and chi, ec and inf), \>470 ms (ad and ado F), Additional-absolute (category 3): \>=500 ms (AAR), Borderline increase (category 4): 30-60 ms (AAR), Prolonged increase (category 5): \> 60 ms (AAR).

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Number of Participants With PCSA in Electrocardiogram (ECG) Heart rate: High	0 Participants	3 Participants
Number of Participants With PCSA in Electrocardiogram (ECG) Heart rate: Low	1 Participants	2 Participants
Number of Participants With PCSA in Electrocardiogram (ECG) PR duration: High	0 Participants	6 Participants
Number of Participants With PCSA in Electrocardiogram (ECG) QTcB: Category 1	5 Participants	13 Participants
Number of Participants With PCSA in Electrocardiogram (ECG) QTcB: Category 2	5 Participants	8 Participants
Number of Participants With PCSA in Electrocardiogram (ECG) QTcB: Category 3	0 Participants	0 Participants
Number of Participants With PCSA in Electrocardiogram (ECG) QTcB: Category 4	5 Participants	7 Participants
Number of Participants With PCSA in Electrocardiogram (ECG) QTcB: Category 5	2 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 90 (pre-infusion)

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Plasma samples were collected to evaluate ceramide levels for safety biomarker analysis. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=4 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
For Adults: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 90	-65.66 percent change Standard Deviation 12.58	—

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 66 (pre-infusion)

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Plasma samples were collected to evaluate ceramide levels for safety biomarker analysis. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
For Pediatrics: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 66	-69.16 percent change Standard Deviation 10.04	—

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 36

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

Liver biopsy samples were evaluated for sphingomyelin accumulation and liver pathology in the participants who previously participated in the DFI13412 study who were at least 18 years old when they entered in this study. Sphingomyelin accumulation was quantified in liver by computer morphometry of high-resolution light microscopy images. Fibrosis grading was assessed on the Laennec scoring system, which grades the extent of fibrosis on a scale from 0 to 4 (0=none; 1=minimal; 2=mild; 3=moderate; 4=cirrhosis). Higher score indicated more severity.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Baseline: Stage 0	1 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Baseline: Stage 1	1 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Baseline: Stage 2	2 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Baseline: Stage 3	1 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Baseline: Stage 4	0 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Month 36: Stage 0	0 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Month 36: Stage 1	1 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Month 36: Stage 2	1 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Month 36: Stage 3	2 Participants	—
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy Month 36: Stage 4	1 Participants	—

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study), Week 2 and Months 12, 18 and 24

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

Liver ultrasound doppler was performed for pediatric participants transitioning from DFI13803 to document hepatic blood flow characteristics, principally portal vein pressure, and blood flow direction. The parameters evaluated were liver dysmorphic findings, liver surface abnormalities, mild ascites and hepatic steatosis. Liver ultrasound Doppler was performed using methods that were compatible with the standard institutional procedures of the investigational site.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=20 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Liver dysmorphic findings: Month 24	0 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Liver surface abnormalities: Baseline	5 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Liver surface abnormalities: Month 12	0 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Mild ascites: Baseline	3 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Liver dysmorphic findings: Baseline	6 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Liver dysmorphic findings: Month 12	3 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Liver dysmorphic findings: Month 18	1 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Mild ascites: Week 2	2 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Mild ascites: Month 12	0 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Hepatic steatosis: Baseline	1 Participants	—
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler Hepatic steatosis: Month 12	0 Participants	—

PRIMARY outcome

Timeframe: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

Blood samples were collected for the presence of ADAs against olipudase alfa. Treatment-boosted ADA: Positive ADA status positive at baseline (pre-existing ADA) and ADA titer level anytime post-baseline significantly higher than that at baseline. Transient ADA: Treatment-induced ADA detected only at 1 sampling time point post-baseline and treatment-induced ADA detected at 2 or more sampling time points post-baseline, where first and last ADA-positive samples (irrespective of any negative samples in between) separated by period of less than 16 weeks, and participant's last sampling time point was ADA-negative. Persistent ADA response: Treatment-induced ADA detected at 2 or more sampling time points post-baseline, where first and the last ADA-positive on-treatment sample (irrespective of any negative samples in between) separated by at least 16 weeks. Treatment-induced: ADA detected in the last 2 sampling time points, irrespective of the time period in between.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa Transient ADA response	0 Participants	1 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa ADA positive since first dose of olipudase alfa	3 Participants	15 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa Treatment-emergent ADA	3 Participants	15 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa ADA positive at baseline	0 Participants	2 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa Treatment-induced ADAs	3 Participants	14 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa Indeterminate ADA response	0 Participants	0 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa Persistent ADA response	3 Participants	12 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa Treatment-boosted ADAs	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study), Month 102 for adults and Month 84 for pediatrics

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Spleen and liver volumes were assessed by abdominal magnetic resonance imaging (MRI) collected and read centrally by a third party blinded to participant number and study visit to quantify the degree of splenomegaly and hepatomegaly at specified time points. Spleen/Liver volume in multiples of normal (MN) = Spleen/Liver volume (cubic centimeter \[cm\^3\]) / \[2xweight (kg)\] where weight was the available value closest to the MRI scan date. Negative value signifies reduction of volume. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=7 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Percent Change From Baseline in Spleen and Liver Volumes at Month 102 for Adults and Month 84 for Pediatrics Spleen volume	-63.60 percent change Standard Deviation 6.34	-75.56 percent change Standard Deviation 7.15
Percent Change From Baseline in Spleen and Liver Volumes at Month 102 for Adults and Month 84 for Pediatrics Liver volume	-46.71 percent change Standard Deviation 14.40	-59.55 percent change Standard Deviation 14.26

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study), Month 102 for adults and Month 84 for pediatrics

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Pulmonary imaging of chest using HRCT was obtained for qualitative assessment of ground glass appearance, interstitial lung disease, pleural thickening and reticulo-nodular density. Images were collected and read centrally by a third party blinded to participant number and study visit. Lung fields were scored subjectively for degree of diffuse lung disease (infiltrative lung disease) in scale of 0-3 ranging from 0 = No disease, 1 = Mild (affecting 1% to 25% of the lung volume), 2 = Moderate (affecting 26% to 50% of the lung volume), 3 = Severe (affecting 51% to 100% of the lung volume) where higher scores indicated more severity. The score of each participant was averaged over all 4 levels and both sides of lung. Mean score across 4 levels and both lungs = (Mean score across X levels for left lung + Mean score across X levels for right lung)/2. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=4 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=5 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Change From Baseline in Pulmonary Imaging by High Resolution Computed Tomography (HRCT) at Month 102 for Adults and Month 84 for Pediatrics Ground Glass Appearance	-1.21 score on a scale Standard Deviation 0.94	-0.42 score on a scale Standard Deviation 0.41
Change From Baseline in Pulmonary Imaging by High Resolution Computed Tomography (HRCT) at Month 102 for Adults and Month 84 for Pediatrics Interstitial Lung Disease	-1.66 score on a scale Standard Deviation 1.20	-1.35 score on a scale Standard Deviation 1.27
Change From Baseline in Pulmonary Imaging by High Resolution Computed Tomography (HRCT) at Month 102 for Adults and Month 84 for Pediatrics Pleural Thickening	0 score on a scale Standard Deviation 0	0 score on a scale Standard Deviation 0
Change From Baseline in Pulmonary Imaging by High Resolution Computed Tomography (HRCT) at Month 102 for Adults and Month 84 for Pediatrics Reticulo-nodular Density	-2.19 score on a scale Standard Deviation 1.07	-1.20 score on a scale Standard Deviation 1.30

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study), Month 78 for adults and Month 84 for pediatrics

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

DLco was used to measure gas exchange across the alveolocapillary membrane. Percent predicted hemoglobin-adjusted DLco was calculated as: 100 x Adjusted DLco/Predicted DLco in unit of mL co/minute (min)/mmHg where, adjusted DLco = Observed DLco (in mL co/min/mmHg) divided by Hemoglobin-adjusted factor. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=5 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Percent Change From Baseline in Percent Predicted Diffusing Capacity of Lungs For Carbon Monoxide (DLco) (Hemoglobin-Adjusted) at Month 78 for Adults and Month 84 for Pediatrics	55.29 percent change Standard Deviation 48.08	46.20 percent change Standard Deviation 48.46

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study), Month 90 for adults (pre-infusion) and Month 78 for pediatrics (pre-infusion)

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Blood samples were collected at specified timepoints for the estimation of platelet count as ASMD is known to result in hematologic disorders. Baseline was defined as the average of all available values before the start of first infusion from original study

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=4 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=5 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Percent Change From Baseline in Platelet Count at Month 90 for Adults and Month 78 for Pediatrics	21.83 percent change Standard Deviation 17.89	63.97 percent change Standard Deviation 32.67

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study), Month 90 for adults and Month 66 for pediatrics

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Blood samples were collected at specified timepoints for fasting lipids as ASMD leads to progressive accumulation of lipids. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=4 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=5 Participants Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Percent Change From Baseline in Low-density Lipoprotein at Month 90 for Adults and Month 66 for Pediatrics	-24.51 percent change Standard Deviation 11.05	-37.30 percent change Standard Deviation 15.68

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 78

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints for each specified category are reported.

The BFI involves a total of 9 items:3 of which measure BFI-fatigue severity score and 6 of which measure BFI-fatigue interference score. Score for each item measuring severity score is assessed by numerical rating scale (NRS); ranges from 0-10 from 0 (no fatigue) to 10 (worst imaginable fatigue) ultimately leading to overall severity score that ranges from 0-30. Respectively, amount that fatigue interfered with different aspects of participant's life during preceding 24 hours (general activity,mood,walking ability,normal work,relations with other people,and enjoyment of life) is captured as part of interference score.These different aspects are measured in scores ranging from 0:does not interfere and 10:completely interferes,ultimately leading to overall interference score ranging between 0-60. Higher scores in both categories mentioned below indicate worse outcome; mean is presented. Baseline was defined as last available non-missing value prior to first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Participants From Adult Study DFI13412: Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire at Month 78 BFI-Fatigue Severity Scale Score	-0.9 score on a scale Standard Deviation 1.92	—
Participants From Adult Study DFI13412: Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire at Month 78 BFI-Fatigue Interference Scale Score	0.6 score on a scale Standard Deviation 2.91	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 78

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

The BPI-SF is a 15-item, validated, self-administered questionnaire designed to measure participant's perceived level of pain. The BPI-SF measured the participant's intensity of pain (sensory dimension), the interference of pain in participant's life (reactive dimension), and asked participant about pain relief, pain quality, and perception of cause of pain. Scoring was based on 4 out of 8 questions in pain severity domain, and 7 questions in pain interference domain, which used numerical rating scale. Pain severity response ranged from 0 = "No pain" to 10 = "Pain as bad as you can imagine". Pain interference response ranged from 0 = "Does not interfere" to 10 = "Completely interferes". Scores were averaged and mean is presented here. Higher scores indicated greater intensity of pain. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Participants From Adult Study DFI13412: Change From Baseline in Brief Pain Inventory-Short Form (BPI-SF) Questionnaire at Month 78 BPI-SF: Pain Severity Scale Score	-1.5 score on a scale Standard Deviation 1.74	—
Participants From Adult Study DFI13412: Change From Baseline in Brief Pain Inventory-Short Form (BPI-SF) Questionnaire at Month 78 BPI-SF: Pain Interference Scale Score	0.7 score on a scale Standard Deviation 3.13	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 78

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study.

The CRQ-SAS is a validated, self-administered questionnaire designed to evaluate health related quality of life (HRQoL) in adults with chronic airflow limitation, chronic respiratory disease and cystic fibrosis. It had 20 items and evaluated 4 dimensions of respiratory impairment (dyspnea, emotional function, fatigue and participant's feeling of control over the disease \[mastery\]). Each domain was measured on 7-point-scale, with 8 reserved for "not done" (1: worst and 7: best). Each domain score was calculated separately. Scores for each question of each domain were added together and divided by number of questions answered in each domain. Only items answered were scored. Mean of average score of completed items is reported. Higher scores indicated better HRQoL in each domain. Baseline was defined as last available non-missing value prior to first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Participants From Adult Study DFI13412: Change From Baseline in Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) at Month 78 Mastery Scale Score	-0.5 score on a scale Standard Deviation 0.91	—
Participants From Adult Study DFI13412: Change From Baseline in Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) at Month 78 Dyspnea Scale Score	0.3 score on a scale Standard Deviation 0.59	—
Participants From Adult Study DFI13412: Change From Baseline in Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) at Month 78 Emotional Function Scale Score	0.2 score on a scale Standard Deviation 1.49	—
Participants From Adult Study DFI13412: Change From Baseline in Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) at Month 78 Fatigue Scale Score	0.3 score on a scale Standard Deviation 0.82	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 72

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

PedsQL included a child self-report for participants 5 to 18 years and parents' report of participants from 2 to 18 years. Child-reported: 23-item PedsQL Generic Core Scales report included 4 scales, physical functioning, emotional functioning, social functioning, and school functioning. Parent-reported: 21-item PedsQL Generic Core Scales report and included similar scales as above. Each item used a 5-point rating scale (from 0=never to 4=almost always). Items are reverse scored and linearly transformed to a 0 (almost always) -100 (never) scale. All summary/total scores were mean of specific items where higher score indicated better HRQoL. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Participants From Pediatric Study DFI13803: Change From Baseline in Pediatric Quality of Life (PedsQL) Generic Core Total Scale Score at Month 72 Child-reported	10.4 score on a scale Standard Deviation 19.4	—
Participants From Pediatric Study DFI13803: Change From Baseline in Pediatric Quality of Life (PedsQL) Generic Core Total Scale Score at Month 72 Parent-reported	14.6 score on a scale Standard Deviation 20.1	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 72

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Hand X-ray was performed on participant's left hand, fingers and wrist to assess the bone age. The X-rays were collected and read centrally by a third party blinded to participant number and study visit. At each visit, difference between the bone age and actual age at that visit was calculated. Difference in age in months was calculated as bone age in months minus real age at time of assessment in months. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Participants From Pediatric Study DFI13803: Change From Baseline in Difference Between Bone Age and Actual Age of Participants at Month 72	28.34 month Standard Deviation 24.68	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of original study) and Month 72

Population: Results are based on the Safety analysis set which consisted of all enrolled participants who received at least 1 infusion (partial or total) of olipudase alfa in the current study. Only those participants with data collected at specified timepoints are reported.

Linear growth in pediatric participants was assessed by height Z-scores. Height Z-score, i.e., the height-for-age Z-score, is the number of standard deviations of the actual height of a child from the median height of the children of the corresponding age and sex as determined from the standard sample. A height Z-score of 0 is equal to the median and is considered normal. Negative numbers indicate values lower than the median and positive numbers indicate values higher than the median. For analysis, mean Z-score was calculated and an increase of mean height Z-score from baseline indicated an improvement on growth. Baseline was defined as the last available non-missing value prior to the first infusion in original study.

Outcome measures

Outcome measures
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 Participants Participants continued to receive olipudase alfa at the same dose as at the completion of original study- DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) Participants continued to receive olipudase alfa at the same dose as the completion of original study- DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Participants From Pediatric Study DFI13803: Change From Baseline in Height Z-score at Month 72	2.31 Z-score Standard Deviation 1.34	—

Adverse Events

Olipudase Alfa: Participants From DFI13412 (Adults)

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Olipudase Alfa: Participants From DFI13803 (Pediatrics)

Serious events: 10 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 participants at risk Participants continued to receive olipudase alfa at the same dose as at the completion of original study-DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 participants at risk Participants continued to receive olipudase alfa at the same dose as at the completion of original study-DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
General disorders Pyrexia	80.0% 4/5 • Number of events 97 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	90.0% 18/20 • Number of events 98 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Injury, poisoning and procedural complications Contusion	80.0% 4/5 • Number of events 55 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	45.0% 9/20 • Number of events 148 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Nervous system disorders Headache	100.0% 5/5 • Number of events 178 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	65.0% 13/20 • Number of events 91 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Olipudase Alfa: Participants From DFI13412 (Adults) n=5 participants at risk Participants continued to receive olipudase alfa at the same dose as at the completion of original study-DFI13412 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible.	Olipudase Alfa: Participants From DFI13803 (Pediatrics) n=20 participants at risk Participants continued to receive olipudase alfa at the same dose as at the completion of original study-DFI13803 (up to 3.0 mg/kg) via IV infusion every 2 weeks for 9 years, or until olipudase alfa was commercially accessible, whichever came first, unless the participant decided to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa was commercially accessible. During the study, pediatric participants who reached adult age (18 years old) received the adult infusion volume.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Congenital, familial and genetic disorders Talipes	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	20.0% 1/5 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	0.00% 0/20 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
General disorders Oedema Peripheral	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
General disorders Pyrexia	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	10.0% 2/20 • Number of events 2 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Immune system disorders Anaphylactic Reaction	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Immune system disorders Food Allergy	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Immune system disorders Hypersensitivity	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 2 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Infections and infestations Gastroenteritis	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	10.0% 2/20 • Number of events 2 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Infections and infestations Otitis Media	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Infections and infestations Pharyngitis	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Infections and infestations Pneumonia Mycoplasmal	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Infections and infestations Urinary Tract Infection	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Injury, poisoning and procedural complications Craniofacial Injury	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Injury, poisoning and procedural complications Femur Fracture	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Injury, poisoning and procedural complications Skull Fractured Base	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Investigations Alanine Aminotransferase Increased	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 3 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Investigations Blood Alkaline Phosphatase Increased	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Musculoskeletal and connective tissue disorders Nuchal Rigidity	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma Of Skin	20.0% 1/5 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	0.00% 0/20 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	20.0% 1/5 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	0.00% 0/20 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Nervous system disorders Lethargy	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Nervous system disorders Seizure	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Reproductive system and breast disorders Endometrial Hypertrophy	20.0% 1/5 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	0.00% 0/20 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Reproductive system and breast disorders Ovarian Cyst	20.0% 1/5 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	0.00% 0/20 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Skin and subcutaneous tissue disorders Rash	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.
Vascular disorders Poor Venous Access	0.00% 0/5 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.	5.0% 1/20 • Number of events 1 • From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first Results are based on the Safety analysis set.