Article detail · 2015
A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency
- Year
- 2015
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue New England Journal of Medicine
- Catalog match (ISSN) New England Journal of Medicine
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
BACKGROUND: Lysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients. The primary end point was normalization of the alanine aminotransferase level. Secondary end points included additional disease-related efficacy assessments, safety, and side-effect profile. RESULTS: Substantial disease burden at baseline included a very high level of low-density lipoprotein cholesterol (≥190 mg per deciliter) in 38 of 66 patients (58%) and cirrhosis in 10 of 32 patients (31%) who underwent biopsy. A total of 65 of the 66 patients who underwent randomization completed the double-blind portion of the trial and continued with open-label treatment. At 20 weeks, the alanine aminotransferase level was normal in 11 of 36 patients (31%) in the sebelipase alfa group and in 2 of 30 (7%) in the placebo group (P=0.03), with mean changes from baseline of -58 U per liter versus -7 U per liter (P<0.001). With respect to prespecified key secondary efficacy end points, we observed improvements in lipid levels and reduction in hepatic fat content (P<0.001 for all comparisons, except P=0.04 for triglycerides). The number of patients with adverse events was similar in the two groups; most events were mild and were considered by the investigator to be unrelated to treatment. CONCLUSIONS: Sebelipase alfa therapy resulted in a reduction in multiple disease-related hepatic and lipid abnormalities in children and adults with lysosomal acid lipase deficiency. (Funded by Synageva BioPharma and others; ARISE ClinicalTrials.gov number, NCT01757184.).
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248 citations
OpenAlex cited_by_count (cache / database)
8 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk 2019
- Survival in infants treated with sebelipase Alfa for lysosomal acid lipase deficiency: an open-label, multicenter, dose-escalation study 2017
- Successful sebelipase alfa desensitization in a pediatric patient 2019
- Safety of sebelipase alfa for the treatment of lysosomal acid lipase deficiency 2021
- A rare cause of hepatomegaly in the childhood: Lysosomal acid lipase deficiency 2018
- Folate deficiency in patients with classical galactosemia: a novel finding that needs to be considered for dietary treatments 2018
- Ten-year enzyme replacement therapy in early childhood-onset lysosomal acid lipase deficiency: A case report 2026
- Genel pediatrist gözü ile lizozomal lipid depo hastalıkları 2016