Efficacy and Safety of Lomitapide in Hypercholesterolemia

Background Despite extensive use of statins, patients with hypercholesterolemia, especially homozygous familial hypercholesterolemia (HoFH), do not achieve recommended targets of low-density lipoprotein cholesterol (LDL-C). There is an urgent need for novel options that could reduce proatherogenic lipoprotein cholesterol levels. Lomitapide, a microsomal triglyceride transport protein (MTP) inhibitor, was approved three years ago as an orphan drug for the treatment of patients with HoFH. Objective Our aim was to systematically evaluate the efficacy and safety of lomitapide and to provide guidance for clinicians. Methods We searched the PubMed, Embase, and Cochrane library databases and ClinicalTrials.gov to identify valid studies published before 31 October 2016 that included lomitapide-treated patients who did or did not undergo lipid-lowering therapy. We assessed the quality of different studies. Data were extracted and evaluated for quality by two reviewers. Results Studies reporting lomitapide therapy included one randomized controlled trial, three single-arm studies, and five case reports. In patients with HoFH, lomitapide reduced levels of LDL-C, total cholesterol, apolipoprotein B, and triglycerides with or without other lipid-lowering therapy, including apheresis. In non-HoFH patients with moderate hypercholesterolemia and hypertriglyceridemia, lomitapide also showed favorable effects on changes in LDL-C and triglycerides. However, both HoFH and non-HoFH patients experienced a reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-1). The most common adverse event was gastrointestinal disorder, and others included liver transaminase elevation and hepatic fat accumulation. Long-term use of lomitapide was associated with an increased risk of progressing to steatohepatitis and fibrosis. Conclusions Lomitapide improved most lipid parameters but not HDL-C or ApoA-1 in patients with HoFH and in non-HoFH patients, and gastrointestinal disorders were the most common adverse event. The possible benefits of lomitapide should be further evaluated and viewed against its possible long-term side effects.