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.