Safety and Efficacy of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia (HoFH): Results from the AEGR-733-301 Long-Term Extension Study.

Aim: Lomitapide is an approved lipid-lowering agent indicated as adjunct to low-fat diet and standard lipid-lowering therapies (LLTs) including lipoprotein apheresis for the treatment of homozygous familial hypercholesterolemia (HoFH). Clinical data from Phase 3 studies have demonstrated the prolonged lipid-lowering capacity of lomitapide in patients with HoFH. We assessed the long-term lipid-lowering capacity of daily oral lomitapide in a cohort of Japanese patients with HoFH enrolled in a Phase 3 extension study.

Methods: Five of 8 Japanese HoFH patients completing a 56-week Phase 3 dose-escalation and safety study of lomitapide continued their maximum tolerated dose (MTD) until study drug was approved or commercially available or until treatment was discontinued. Lipid parameters were measured at Day 1 and at 12-week intervals through study end. Safety and tolerability were assessed.

Results: Daily lomitapide treatment with permitted LLTs maintained approximately 50% mean reductions in plasma low-density lipoprotein cholesterol (LDL-C) levels from baseline for ＞60 weeks. Reductions in LDL-C levels varied across patients and were not associated with the HoFH genotype. Four patients achieved ＞25% reductions and 1 patient achieved ＞50% reduction in LDL-C; 2 patients achieved reduction in LDL-C to ＜100 mg/dL. Lomitapide significantly reduced total cholesterol (－26.5%), triglycerides (－54.8%), and non-high-density lipoprotein cholesterol (non-HDL-C) (－37.4%). All 5 patients continued their individual MTD of lomitapide throughout the extension study with acceptable safety and tolerability, and no deaths were reported.

Conclusion: Results from this extension study support the long-term safety and efficacy of lomitapide in significantly reducing plasma levels of atherosclerotic lipids in patients with HoFH.