Clinical Study In Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

A Phase 2, Open Label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Sebelipase Alfa in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency

This was an open-label, repeat-dose, study of sebelipase alfa in infants with rapidly progressive lysosomal acid lipase deficiency (LAL-D). Eligible participants received once-weekly infusions of sebelipase alfa for up to 3 years.

Lysosomal acid lipase deficiency is a rare autosomal recessive lipid storage disorder that is caused by a marked decrease or complete absence of the LAL enzyme, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids in hepatocytes and macrophages leads to hepatomegaly, fibrosis, cirrhosis, liver dysfunction, and hepatic failure. In the small intestine, lipid-laden macrophage accumulation in the lamina propria leads to profound malabsorption.

Lysosomal acid lipase deficiency presenting in infancy is an extremely rare form of the disease characterized by profound malabsorption, growth failure, and hepatic failure that is usually fatal within the first 6 months of life.

Inclusion Criteria:

1. Participant's parent or legal guardian (if applicable) consent to participation in the study

2. Confirmation of documented decreased LAL activity relative to the normal range of the lab performing the assay or confirmation of LAL-D diagnosis as determined by a Sponsor-approved central laboratory

3. Substantial clinical concerns, in the opinion of Investigator and Sponsor, of rapid disease progression requiring urgent medical intervention including, but not restricted to the following:

   • Marked abdominal distension and hepatomegaly
   • Failure to thrive
   • Disturbance of coagulation
   • Severe anemia
   • Sibling with rapidly progressive course of LAL-D

Exclusion Criteria:

1. Clinically important concurrent disease
2. Participant was > 8 months of age at the time of first dosing
3. Participant received an investigational medicinal product other than sebelipase alfa within 14 days prior to the first dose of sebelipase alfa in this study
4. Myeloablative preparation, or other systemic pre-transplant conditioning, for hematopoietic stem cell or liver transplantation
5. Previous hematopoietic stem cell or liver transplant
6. Known hypersensitivity to eggs