Long-term safety and efficacy of lomitapide in patients with homozygous familial hypercholesterolemia: Five-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER)

Abstract

Lomitapide is a lipid-lowering agent indicated as adjunct therapy for homozygous familial hypercholesterolemia (HoFH) in adults. The Lomitapide Observational Worldwide Evaluation Registry is an international, observational registry assessing long-term safety, tolerability, and effectiveness of lomitapide. This analysis examines 5-year data from the registry up to February 28,2019. At lomitapide initiation, enrolled patients (N=187) were a mean±SD age of 52.2±15.3years with a mean±SD low-density lipoprotein cholesterol (LDL-C) measurement of 232.0±94.9mg/dL. Exposure duration was up to 5.9years (median, 1.98years), and median dose was 10mg (range, 5mg QOD to 40mg QD). After treatment, there was a mean 33% reduction in LDL-C (45% in patients remaining on lomitapide), 65.4% achieved LDL-C <100mg/dL, and 41.1% achieved LDL-C <70mg/dL. At year 4, the absolute mean change from baseline in LDL-C was -70.6±76.21mg/dL. Adverse events (AEs) occurred in 75.7% of patients, treatment-related AEs in 54.6%, and serious AEs in 22.2%; 23.2% of patients discontinued because of an AE. Events of special interest included gastrointestinal (13.5%), hepatic (15.1%), major adverse cardiovascular events (10.8%, resulting in 5 deaths), tumors (2.2%), and 4 pregnancies in 3 of 32 women of childbearing potential. The efficacy and safety of lomitapide are consistent with phase III trial data despite using a much lower median dose of 10mg vs 40mg in phase III. No new safety signals were identified. The incidence of AEs, serious AEs, and aminotransferase alanine transaminase elevations was lower than that seen in the phase III trial, potentially related to the lower median dose.