Long-term experience with lomitapide treatment in patients with homozygous familial hypercholesterolemia: Over 10 years of efficacy and safety data.

BACKGROUND

Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by loss of low-density lipoprotein receptor (LDLR) function, an extreme elevation of circulating low-density lipoprotein cholesterol (LDL-C) from birth and substantially reduced life expectancy, if untreated. Patients with HoFH are frequently diagnosed late and have a markedly elevated risk of premature atherosclerotic cardiovascular disease (ASCVD).

SOURCES OF MATERIAL

The current European Atherosclerosis Society consensus statement on the treatment of HoFH recommends an LDL-C goal of <55 mg/dL for adults with ASCVD or major ASCVD risk factors, <70 mg/dL for adults without ASCVD risk factors, and <115 mg/dL for pediatric patients without ASCVD. However, achieving these targets is challenging, necessitating treatment with multiple lipid-lowering therapies in combination, including statins, ezetimibe, and other treatments such as lipoprotein apheresis, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), lomitapide, and evinacumab.

ABSTRACT OF FINDINGS

Lomitapide is a small molecule inhibitor of microsomal triglyceride transfer protein. As lomitapide reduces the production of apolipoprotein B-containing lipoproteins, its mechanism of action is independent of LDLR. The present review summarizes the available evidence regarding the use of lomitapide for the treatment of patients with HoFH.

CONCLUSIONS

Over the last decade, numerous clinical trials, real-world evidence studies, and case studies/series have investigated the LDL-C-lowering efficacy/effectiveness and safety of lomitapide. Lomitapide is an effective treatment option for lowering LDL-C in patients with HoFH who are refractory to LDLR-dependent therapies, such as statins, ezetimibe, and PCSK9i.

Copyright © 2025. Published by Elsevier Inc.