Burton_2022_J.Pediatr.Gastroenterol.Nutr__

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 >8months of age diagnosed with LAL-D received sebelipase alfa 1.0mg/kg by intravenous infusion every other week (qow) for up to 144weeks. Dose escalation to 3.0mg/kg qow and subsequently to 3.0mg/kg weekly was permitted, per protocol; dose reductions for tolerability were permitted to 0.35mg/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 65.5U/L, respectively. Twenty-eight patients completed 96weeks of treatment, and 25 continued into the extended treatment period; 19 completed 144weeks. From baseline to week 144, median ALT and AST levels changed by -42.0 and -22.0U/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 52.6mg/dL, and median high-density lipoprotein cholesterol increased by 9.8mg/dL. Liver biopsies showed mostly improved or stable histopathology at 48 and 96weeks 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.