Abstract 12450: Long-Term Efficacy and Safety of Lomitapide for the Treatment of Homozygous Familial Hypercholesterolemia: Results of the Phase 3 Extension Trial
Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by highly elevated low-density lipoprotein cholesterol (LDL-C) levels and high cardiovascular disease risk. Lomitapide, an oral microsomal triglyceride transfer protein inhibitor, was approved for the treatment of adult HoFH based on a small phase 3 study. We report efficacy and safety results from the phase 3 long-term extension study.
Methods: Eligible HoFH patients completing the 78-wk phase 3 pivotal trial were enrolled into a single-arm extension study where lomitapide was administered daily at the maximum tolerated dose (5-60mg/d) until lomitapide was commercially available in the patient’s country. Concurrent lipid-lowering therapies, including apheresis, were permitted.
Results: Nineteen of 23 patients who completed the pivotal study entered the extension trial (9/19 apheresis) with 16 patients completing all end of study assessments. Mean treatment duration was 4.8 yrs (range 2.1-5.7 yrs, median 5.1 yrs). Lomitapide efficacy was maintained throughout the study (Table). Reported adverse events were similar to those in the pivotal phase 3 study (chiefly gastrointestinal). Five patients (26%) experienced transient alanine aminotransferase (ALT) elevations ≥5x upper limit of normal (ULN) that were successfully managed by dose adjustment in all but one patient who was discontinued due to persistent excessive alcohol use. One 58 year-old patient with known CAD had sudden cardiac death. Median hepatic fat increased by 10% above baseline after 3 yrs and stabilized through the treatment period (Table). No other clinically relevant findings were identified to date.
Conclusions: The long-term efficacy of lomitapide was maintained up to 5.7 yrs in patients completing the phase 3 trial with no new safety signals observed. The clinical significance of the increase in hepatic fat remains unknown.
- Lipid metabolism, inborn errors
- Clinical trial, Phase IV
- Homozygous familial hypercholesterolemia
Author Disclosures: D. Blom: Other Research Support; Modest; Amgen, Aegerion. Honoraria; Modest; MSD, AstraZeneca, Pfizer, Sanofi-Aventis, Amgen, Servier. Consultant/Advisory Board; Modest; AstraZeneca, MSD, Aegerion, Gemphire, Amgen. M. Averna: Consultant/Advisory Board; Modest; Sanofi-Aventis, Synageva, MSD, Amgen, Chesai, Aegerion, Abbott. E. Meagher: None. H. du Toit Theron: None. C. Sirtori: None. R. Hegele: Speakers Bureau; Modest; Amgen, Sanofi, Valeant, Aegerion. Consultant/Advisory Board; Modest; Amgen, Sanofi-Aventis, Valeant, Merck, Pfizer, Aegerion. P. Shah: None. D. Gaudet: Other Research Support; Modest; Cymabay, Gemphyre. Other Research Support; Significant; AstraZeneca, Pfizer, Aegerion, Cerenis, Amgen, Regeneron, Novartis, ISIS. Consultant/Advisory Board; Modest; Amgen, Regeneron, Sanofi-Aventis, Uniquire, Chiesi. Consultant/Advisory Board; Significant; Novartis, ISIS. C. Stefanutti: Speakers Bureau; Modest; Aegerion, Kaneka. G. Vigna: None. P. Foulds: Employment; Significant; Aegerion. L. Bloedon: Employment; Significant; Aegerion. Ownership Interest; Modest; Aegerion. D. Rader: None. M. Cuchel: Other Research Support; Significant; Regeneron, Sanofi. Honoraria; Modest; Aegerion.
- © 2015 by American Heart Association, Inc.