Long‐term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia

Abstract

Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor for patients with homozygous familial hypercholesterolaemia. Due to its mechanism of action, potential hepatic effects of lomitapide are of clinical interest. This study aimed to determine the long-term hepatic safety of lomitapide. Methods: Data were aggregated from the pivotal phase 3 and extension phase clinical trial with lomitapide (median 5.1 years; serum total bilirubin, transaminases, cytokeratin-18 [CK-18] and enhanced liver fibrosis [ELF] score, fat-soluble vitamins and essential fatty acids), 8-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) and real-world evidence from a cohort of patients treated with lomitapide in Italy (hepatic elastography, and FIB-4 score for hepatic fibrosis).Results: In the phase 3 trial and the LOWER registry, any asymptomatic excursions in liver transaminase levels were not associated with elevations in bilirubin, and no Hy's law cases were detected in up to 8 years follow-up. There were no clinically relevant increases among hepatic biomarkers CK-18, CK-18 fragments or ELF score and fatsoluble vitamins and essential fatty acids remained above normal levels. In 34 patients treated in Italy with lomita pide for more than 9 years, elevations in hepatic fat were mild-to-moderate; hepatic stiffness remained normal, and the mean FIB-4 score remained below the fibrosis threshold value of 2.67. Conclusions:These data indicate that the hepatic safety of lomitapide remains favourable with no clinically significant elevations in hepatic biomarkers and hepatic stiffness remained normal for more than 9 years follow-up.

Advances in Treatment of Dyslipidemia

“…The data analysis showed that lomitapide has been associated with temporary elevations in liver transaminases, both alanine aminotransferase (ALT) and aspartate aminotransferase (AST), with no occurrences of increases in bilirubin levels, a moderate buildup of fat in the liver, and elevations in hepatic biomarkers and hepatic stiffness. However, the analysis did not show the clinical impact of lomitapide treatment on liver damage during the long-term study [106].…”

Hypercholesterolemia: A literature review on management using tafolecimab – a novel member of PCSK9 monoclonal antibodies

“…It is a microsomal triglyceride transfer protein (MTP) inhibitor that decreases the formation of very low density lipid chylomicrons and reduces LDL-C levels 84 . Adverse effects are primarily gastrointestinal events, with rare cases of hepatic injury being reported 85 , 86 . Evidence of its long-term safety and efficacy for HoFH patients in European and Japanese studies has been published, although more extensive phase 3 trials are still required 87 – 89 .…”

The importance of LDL-C lowering in atherosclerotic cardiovascular disease prevention: Lower for longer is better

“…The median dose used was 40 mg, however, it has been shown to achieve equivalent LDL-C lowering effects or greater at lower doses [77] . Although lomitapide is linked to an increase in hepatic steatosis, a study aiming to explore the long-term hepatic safety of lomitapide found no clinically significant elevations in hepatic biomarkers, and hepatic stiffness remained normal for over 9-years of follow-up [78] .…”