Review of the long-term safety of lomitapide: a microsomal triglycerides transfer protein inhibitor for treating homozygous familial hypercholesterolemia

ABSTRACT

Introduction: Homozygous familial hypercholesterolemia (HoFH) is a rare and life-threatening lipid disorder characterized by extremely elevated low-density lipoprotein-cholesterol (LDL-C) concentrations and premature atherosclerotic cardiovascular disease (CVD). Conventional lipid-lowering agents remain insufficient in managing this disease, which emphasize the unmet medical need for potential therapies capable of lowering LDL-C and decreasing CVD risk in this patient population.

Areas covered: Novel LDL receptor (LDLR) independent drugs have been recently approved or are in development for the treatment of HoFH, including lomitapide (Juxtapid®). This oral microsomal triglyceride transfer protein (MTP) inhibitor was approved in 2012 in several countries as an adjunct to a low-fat diet and other lipid-lowering drugs with or without LDL apheresis to treat patients with HoFH. This review summarizes key safety and efficacy data of lomitapide from clinical trials and ‘real-life’ experience.

Expert opinion: While lomitapide is an interesting therapy for treating HoFH, long-term safety, as well as cardiovascular outcome data, are yet to be provided. Precision medicine has recently contributed to the development of several agents designed to address the unmet medical need of HoFH. However, combining safety, efficacy, accessibility, and affordability in a single therapy constitutes very challenging individual and societal paradigms in HoFH treatment.

KEYWORDS:

• Lomitapide
• safety
• homozygous familial hypercholesterolemia
• rare lipid disorders

Article highlights

• Homozygous familial hypercholesterolemia (HoFH) presents a severe FH phenotype typically associated with premature CVD occurring in early twenties or even earlier for untreated patients.

• Lomitapide (Juxtapid®) is a first-in-class microsomal triglyceride transfer protein (MTP) inhibitor that shows significant improvements in lipid parameters over long-term treatment in HoFH.

• Long-term treatment with lomitapide shows increased risk of hepatotoxicity, accumulation of hepatic fat, common GI-related side-effects and impairment in fat-soluble vitamins and fatty acids absorption in patients with HoFH.

• Continuous monitoring of hepatic fat accumulation is recommended when using lomitapide in clinical practice.

• In order to be clinically used in HoFH, therapeutic agents should address the unmet medical need for this serious life-threatening condition while being a safe, effective, accessible and affordable treatment.

This box summarizes key aspects of this article

Declaration of interest

D Gaudet has been involved as a principal investigator or consultant in pivotal trials in HoFH developed by Regeneron, Sanofi, Amgen, Aegerion, Gemphire, HDL Therapeutics, Cerenis, and Cymabay. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have served as an advisory board member for Aegerion (manufacturer of lomitapide). The reviewer has received honoraria from Aegerion to attend advisory board meetings and for lectures, and travel support to attend scientific meetings. The reviewer is on the steering committee of the LOWER trial. All other peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.