Lysosomal acid lipase deficiency can cause cirrhosis and severe dyslipidemia. Burton et al. recently published in N Engl J Med a multicenter, randomized, double-blind, placebo-controlled study involving 66 patients with lysosomal acid lipase deficiency. This was a phase 3 clinical trial of enzyme-replacement therapy in children and adults, using sebelipase alfa.
Sebelipase alfa was administered intravenously (1 mg per kg; every other week) and the primary end point was normalization of the alanine aminotransferase level. Secondary end points included, lipid levels, fat content, as well as, safety and side-effect profile. The placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients.
A total of 65 of the 66 patients who underwent randomization completed the trial. 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). Lipid levels and hepatic fat content improved (P<0.001) for all comparisons, except for triglycerides (P=0.04). No adverse events related to treatment were identified.
A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency. Burton BK et al. N Engl J Med. 2015 Sep 10;373(11):1010-20. doi: 10.1056/NEJMoa1501365. PMID: 26352813
Posted by Yannis Trakadis, MD