Abstract 12468: Efficacy and Safety of Lomitapide in Japanese Patients With Homozygous Familial Hypercholesterolemia on Concurrent Lipid-Lowering Therapy

Abstract

Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor indicated as an adjunctive therapy for adults with homozygous familial hypercholesterolemia (HoFH). In a previous global Phase 3 study in non-Japanese patients with HoFH, lomitapide in combination with other lipid-lowering therapy resulted in a 50% reduction in LDL-C levels from baseline after 26 weeks of treatment. This open-label, multicenter, phase 3 study evaluated the efficacy and safety of lomitapide in adult Japanese patients with HoFH. Methods: Adult patients with HoFH added lomitapide to their maximally tolerated, stable lipid-lowering therapy. Lomitapide was initiated at 5 mg/day and escalated to each patient’s maximum tolerated dose (≤60mg/day) over 14 weeks. The primary endpoint was the mean % change from baseline in LDL-C at Week 26. Results: Nine patients (5 men, 4 women, mean age 50 [33-74] years) received lomitapide (mean dose 20 mg); 8 patients completed 26 weeks of treatment. Mean LDL-C was reduced from 199.3 mg/dL (95% CI: 148.6-250.0) at baseline to 117.9 mg/dL (95% CI: 70.2-165.6, last observation carried forward) at Week 26. Mean % LDL-C reduction was significant in patients with and without apheresis; significant reductions were also seen in key secondary endpoints (Table). A >50% reduction in LDL from baseline was achieved by 5/9 (56%) patients. Gastrointestinal symptoms were the most common adverse event (diarrhea in 7/9 [78%] patients). Abnormal liver function tests were reported in 3/9 (33%) patients; 1 patient discontinued treatment after 22 weeks due to persistent liver enzyme elevations. There were no serious adverse events. Conclusions: The efficacy and safety of 26 weeks of lomitapide in Japanese patients were consistent with results in the global phase 3 study, including a significant reduction in LDL-C and no new safety signals. Treatment in the safety phase (Weeks 26-56) is ongoing.