https://pubmed.ncbi.nlm.nih.gov/35442238/ Metabolic

J Pediatr Gastroenterol Nutr. 2022 Apr 20.
doi: 10.1097/MPG.0000000000003452.Online ahead of print
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Long-term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency

Barbara K Burton 1, Alejandra Consuelo Sanchez 2, Maria Kostyleva 3, Ana Maria Martins 4, Sachin Marulkar 5, Florian Abel 5, Ivo Barić 6
Abstract

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 due to liver transplant (unrelated to treatment). Two patients tested positive for non-neutralizing, anti-drug antibodies on 1 occasion each.

Conclusion: Sebelipase alfa was well tolerated and resulted in sustained improvements in liver and lipid parameters.