Lomitapide 5mg capsules

AimsHomozygous familial hypercholesterolaemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth. This review aimed to critically evaluate treatments for HoFH with respect to their efficacy, safety, accessibility, overall context and position within the treatment pathway.Methods and resultsA mixed-methods review was undertaken to systematically identify and characterize primary interventional studies on HoFH, with a focus on LDL-C reduction as the primary outcome. Interventions assessed were ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), lomitapide, evinacumab, with or without LDL apheresis. Twenty-six seminal studies reporting unique patient data were identified. Four studies were randomized controlled trials (RCTs) with the remainder being single-arm trials or observational registries. Data extracted were heterogeneous and not suitable for meta-analyses. Two RCTs, assessed at being low risk of bias, demonstrated PCSK9i were safe and moderately effective. A randomized controlled trial (RCT) demonstrated evinacumab was safe and effective in all HoFH subgroups. Lomitapide was reported to be efficacious in a single-arm trial, but issues with adverse events, tolerability, and adherence were identified. An RCT on ezetimibe showed it was moderately effective when combined with a statin. LDL apheresis was reported as effective, but its evidence base was at very high risk of bias. All interventions lowered LDL-C, but the magnitude of this, and certainty in the supporting evidence, varied.ConclusionIn practice, multiple treatments are required to treat HoFH. The sequencing of these should be made on an individualized basis, with consideration made to the benefits of each intervention.

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Purpose Homozygous Familial Hypercholesterolemia (HoFH) is a rare and life-threatening genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset atherosclerotic cardiovascular disease. Lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor, decreases LDL-C independent of LDL receptor function, providing an alternative treatment in this population. We aimed to evaluate the efficacy and safety of lomitapide in patients with HoFH through a systematic review and meta-analysis of available clinical evidence. Methods A comprehensive search was conducted in PubMed, Scopus, and Web of Science through March 2025. Observational studies and clinical trials reporting on lipid profile changes and safety outcomes in HoFH patients receiving lomitapide were included. Outcomes were pooled using random-effects models, and heterogeneity was assessed using the I2 statistic. Results Eight studies comprising both adult and pediatric patients (n = 209) were included. Lomitapide significantly reduced LDL-C levels by 49.27%, total cholesterol by 46.05%, and apolipoprotein B by 51.01%. Reductions were also observed in triglycerides, VLDL-C, and non–HDL-C. HDL-C remained relatively unchanged. Adverse events were mostly gastrointestinal, with a 14% discontinuation rate. The overall quality of studies ranged from fair to good. Conclusions Lomitapide demonstrates substantial efficacy in reducing LDL-C and other atherogenic lipids in HoFH patients, with an acceptable safety profile. These findings support its role as an adjunctive therapy in this population, though further randomized controlled trials are warranted to validate long-term safety and effectiveness. Supplementary Information The online version contains supplementary material available at 10.1007/s10557-025-07764-4.

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Abstract Lomitapide is an inhibitor of MTP, an enzyme located in the endoplasmic reticulum of hepatocytes and enterocytes. This enzyme is responsible for the synthesis of very low-density lipoproteins in the liver and chylomicrons in the intestine. Lomitapide has been approved by the US Food and Drug Administration, European Medicines Agency, and other regulatory agencies for the treatment of hypercholesterolemia in adult patients with homozygous familial hypercholesterolemia. Clinical trials have shown that lomitapide reduces low-density-lipoprotein cholesterol levels by around 40% in homozygous familial hypercholesterolemia patients on treatment with statins with or without low-density-lipoprotein apheresis, with an acceptable safety and tolerance profile. The most common adverse events are gastrointestinal symptoms that decrease in frequency with long-term treatment, and the increase in liver fat remains stable. This review analyzes the clinical use, efficacy, and tolerability of lomitapide.

Abstract licence: CC BY-NC 3.0

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.

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