Abstract 12117: Global Real-World Data on the Use of Lomitapide in Treating Homozygous Familial Hypercholesterolemia: The Lomitapide Observational Worldwide Evaluation Registry (LOWER), Two-Year Data
Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor indicated as adjunctive therapy for adults with homozygous familial hypercholesterolemia (HoFH). LOWER is a global observational registry to prospectively assess long-term, safety and effectiveness of lomitapide in clinical practice. Adult HoFH patients treated with lomitapide in clinical practice are eligible.
Results: As of March 1, 2016, 143 patients had been enrolled in the USA, Canada, EU and Taiwan (Table); 139 patients had lomitapide exposure data (median 17.7 months, range 0.3-35.9 months). Globally, median lomitapide dose was 10 mg QD (range 5 mg QOD-40 mg QD, 6-33 months). A ≥ 50% reduction in LDL-C at any time post-baseline was measured in 58% of patients; 62% of patients achieved LDL-C < 100 mg/dL and 37% achieved LDL-C < 70 mg/dL. AEs were experienced by 73% of patients; GI disorders were the most common (45%). Serious AEs occurred in 21 (15%) patients. Thirty-three (24%) patients discontinued lomitapide because of an AE. Events of special interest comprised: major adverse cardiovascular events (11 patients, resulting in 2 deaths); hepatic events (19 patients, 6 discontinuations); GI events (20 patients, 16 discontinuations); oncologic events (2 patients: 1 pancreatic mass [diagnosis unconfirmed], 1 mediastinal B-cell lymphoma); 1 pregnancy; no coagulopathy events. Liver function tests were always performed per the label in 48% of patients. Peak ALT and AST was normal in 35% of patients and ≥ 3x ULN in 21% (among which 5% had ≥ 5x - <10x ULN). No cases of Hy’s Law were recorded.
Conclusions: The LOWER registry demonstrated safety and efficacy consistent with product labeling in patients treated with lomitapide for up to 3 years, but efforts are needed to improve prescriber adherence to recommended hepatic safety monitoring. There were no new safety signals and LDL-C reduction was consistent and robust, with 62% of patients achieving LDL-C < 100 mg/dL.
Author Disclosures: J. Underberg: Research Grant; Modest; Aegerion Pharmaceuticals, Pfizer. Speakers Bureau; Modest; AstraZeneca, Merck. Speakers Bureau; Significant; Alexion/Synageva, Amgen, Regeneron. Consultant/Advisory Board; Modest; Kowa Pharmaceuticals, Amgen, Aegerion Pharmaceuticals, Sanofi, Regeneron, Akcea, Amarin, AstraZeneca, Eli Lilly, Alexion, Synageva, Recombine. Other; Modest; Aegerion Pharmaceuticals. C. Cannon: Research Grant; Significant; Arisaph, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Merck, Takeda. Consultant/Advisory Board; Modest; Alnylam, Amgen, Arisaph, Boehringer Ingelheim, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, GlaxoSmithKline, Kowa, Merck, Takeda, Pfizer. Consultant/Advisory Board; Significant; Lipimedix, Regeneron, Sanofi. Other; Modest; Aegerion Pharmaceuticals. D. Larrey: Consultant/Advisory Board; Modest; Aegerion Pharmaceuticals. Other; Modest; Aegerion Pharmaceuticals, Sanofi. L. Makris: Other; Modest; Aegerion Pharmaceuticals. C. Schwamlein: Other; Modest; Aegerion Pharmaceuticals. H. Phillips: Employment; Significant; Aegerion Pharmaceuticals. Ownership Interest; Modest; Aegerion Pharmaceuticals. L. Bloeden: Employment; Significant; Aegerion Pharmaceuticals. Other; Modest; Aegerion Pharmaceuticals. D. Blom: Consultant/Advisory Board; Modest; Aegerion Pharmaceuticals, Amgen, MSD, Sanofi. Other; Modest; Aegerion Pharmaceuticals.
- © 2016 by American Heart Association, Inc.