Long-term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia.

AbstractIntroduction: 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, cytokera-tin- 18 [CK-18] and enhanced liver fibrosis [ELF] score, fat-soluble vitamins and essen-tial 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 fat- soluble 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 re-mained below the fibrosis threshold value of 2.67.Conclusions: These data indicate that the hepatic safety of lomitapide remains fa-vourable with no clinically significant elevations in hepatic biomarkers and hepatic stiffness remained normal for more than 9 years follow-up.Phase 3 trial: NCT00730236; extension phase: NCT00943306; LOWER: NCT02135705