Safety and Efficacy Study of Sebelipase Alfa in Participants With Lysosomal Acid Lipase Deficiency

A Multi-Center, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency

This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D).

The primary objective of this study was to evaluate the safety of intravenous (IV) infusions of sebelipase alfa in a more broad population of LAL-D participants than previously studied. Such participants may have been excluded from enrollment in other studies of LAL-D because of age, disease progression, previous treatment by hematopoietic stem cell or liver transplantation, less common disease manifestations, or disease characteristics that would preclude participation in a placebo-controlled study. This open-label study included infants >8 months, children, and adults. At least 4 participants in the study were to be between the age of 2 and 4 years. Eligible participants received sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) every other week (qow).

Key Inclusion Criteria:

1. Participant was >8 months of age at the time of dosing.

2. Confirmation of LAL-D diagnosis as determined by the central laboratory or, for participants with prior hematopoietic stem cell transplant or liver transplant, historical enzyme activity or molecular genetic testing confirming a diagnosis of LAL-D.

3. Participants >8 months but <4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:

   • Dyslipidemia
   • Elevated transaminases
   • Impaired growth
   • Suspected malabsorption
   • Other clinical manifestation of LAL-D

4. Participants ≥4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:

   • Evidence of advanced liver disease
   • Histologically confirmed disease recurrence in participants with past liver or hematopoietic transplant
   • Persistent dyslipidemia
   • Suspected malabsorption
   • Other clinical manifestation of LAL-D

Key Exclusion Criteria:

1. Participant had known causes of active liver disease other than LAL-D, which had not been adequately treated.
2. Participant received a hematopoietic stem cell or liver transplant <2 years from the time of dosing.
3. Participant with co-morbidities other than complications due to LAL-D, which were irreversible or associated with a high mortality risk within 6 months or would interfere with study compliance or data interpretation.