Efficacy and Safety of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia

Abstract

Aim: There is an unmet need in Japan for more optimal lipid-lowering therapy (LLT) for patients with homozygous familial hypercholesterolemia (HoFH) who respond inadequately to available drug therapies and/or apheresis, to achieve goals of low-density lipoprotein cholesterol (LDL-C) reduction by 50% or to < 100 mg/dL.Methods: In this study, Japanese patients with HoFH on stable LLT and diet were treated with lomitapide, initiated at 5 mg/day and escalated to maximum tolerated dose (up to 60 mg/day) over 14 weeks. The primary efficacy endpoint was mean percentage change from baseline to Week 26 in LDL-C. Secondary endpoints included changes in other lipid parameters and safety throughout the 56-week study (including follow-up).Results: Nine patients entered the efficacy phase of the study and, of these, eight completed 56 weeks. Mean LDL-C was reduced by 42% (p < 0.0001) at 26 weeks, from 199 mg/dL (95% CI: 149–250) at baseline to 118 mg/dL (95% CI: 70–166). A 50% reduction in LDL-C and LDL-C < 100 mg/dL was achieved by five and six of nine patients, respectively, at 26 weeks. After 56 weeks, LDL-C was reduced by 38% (p = 0.0032) from baseline. Significant reductions in non-HDL-C, VLDL-C, triglycerides, and apolipoprotein B were also reported at Week 26. There were no new safety signals and, similar to previous studies, gastrointestinal adverse events were the most common adverse events.Conclusion: Lomitapide, added to ongoing treatment with other LLTs, was effective in rapidly and significantly reducing the levels of LDL-C and other atherogenic apolipoprotein B-containing lipoproteins in adult Japanese patients with HoFH.

Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017

“…A retrospective study found that the administration of statin and other drugs was effective in reducing mortality rates in HoFH 883 ) . It has been reported that MTP inhibitors, which were developed for HoFH patients, lowered LDL-C by approximately 50% 693 , 884 ) . However, as the frequencies of the adverse events of fatty liver and diarrhea are high, it is essential to control the fat and alcohol intake strictly.…”

Guidance for Pediatric Familial Hypercholesterolemia 2017

“…The microsomal triglyceride transfer protein inhibitor, lomitapide, is an orally administered agent and the mechanism underlying its LDL-C lowering effect is independent of LDL receptor activation. However, abdominal pain, diarrhea, liver dysfunction and fatty liver have been reported as adverse effects of this drug and although it has been already approved for use in adult patients with HoFH in Japan, it is not approved for childhood HoFH at present 40 , 41 ) .…”

Statement for Appropriate Clinical Use of PCSK9 Inhibitors

“…When ineffective, useless continuation of PCSK9 inhibitors is not advisable, and genetic testing should be considered for the possibility of FH homozygote 5 ) . If the diagnosis is FH homozygote, consider treatment not dependent on LDL receptor function such as MTP inhibitors 6 ) (after obtaining authorization for treatment of designated intractable disease) and LDL apheresis.…”