Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency

Barbara K. Burton, Alejandra Consuelo Sanchez, Maria Kostyleva, Ana Maria Martins, Sachin Marulkar, Florian Abel, Ivo Barić

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


OBJECTIVES: Sebelipase alfa is approved for treatment of lysosomal acid lipase deficiency (LAL-D). This single-arm, open-label study (NCT02112994) evaluated sebelipase alfa efficacy and safety in patients with LAL-D. METHODS: Patients >8 months of age diagnosed with LAL-D received sebelipase alfa 1.0 mg/kg by intravenous infusion every other week (qow) for up to 144 weeks. Dose escalation to 3.0 mg/kg qow and subsequently to 3.0 mg/kg weekly was permitted, per protocol; dose reductions for tolerability were permitted to 0.35 mg/kg qow. Descriptive statistical analyses were conducted. RESULTS: Thirty-one patients were enrolled and treated. Baseline median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were 63.5 and 65.5 U/L, respectively. Twenty-eight patients completed 96 weeks of treatment, and 25 continued into the extended treatment period; 19 completed 144 weeks. From baseline to week 144, median ALT and AST levels changed by -42.0 and -22.0 U/L, respectively, median liver and spleen volumes changed from 1.4 to 1.3 and from 2.6 to 2.3 multiples of normal, respectively, median low-density lipoprotein cholesterol levels decreased by 52.6 mg/dL, and median high-density lipoprotein cholesterol increased by 9.8 mg/dL. Liver biopsies showed mostly improved or stable histopathology at 48 and 96 weeks versus baseline. Infusion-associated reactions were mild (n = 1) or moderate (n = 2). One patient (a candidate for liver transplant at baseline) discontinued treatment because of liver transplant (unrelated to treatment). Two patients tested positive for nonneutralizing, anti-drug antibodies on 1 occasion each. CONCLUSION: Sebelipase alfa was well tolerated and resulted in sustained improvements in liver and lipid parameters.

Original languageEnglish (US)
Pages (from-to)757-764
Number of pages8
JournalJournal of pediatric gastroenterology and nutrition
Issue number6
StatePublished - Jun 1 2022

ASJC Scopus subject areas

  • Gastroenterology
  • Pediatrics, Perinatology, and Child Health


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