Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

IntroductionHomozygous familial hypercholesterolaemia (HoFH) is a rare, autosomal disease affecting the clearance of low-density lipoprotein cholesterol (LDL-C) from circulation, and leading to early-onset atherosclerotic cardiovascular disease (ASCVD). Treatment consists mainly of statins, lipoprotein apheresis (LA) and, more recently, the microsomal triglyceride transfer protein inhibitor lomitapide. Lomitapide is not licensed for use in children, but has been made available through an expanded access programme or on a named patient basis.MethodsThis case series includes 11 HoFH patients in 10 different centres in eight countries, less than 18years of age (mean 11.61.1years, 64% male), with signs of ASCVD, and who have received treatment with lomitapide (mean dose 24.54.3mg/day; mean exposure 20.02.9months). Background lipid-lowering therapy was given according to local protocols. Lomitapide was commenced with a stepwise dose escalation from 2.5mg or 5mg/day; dietary advice and vitamin supplements were provided as per the product label for adults. Laboratory analysis was conducted as part of regular clinical care.Results In the 11 cases, mean baseline LDL-C was 419 +/- 74.6mg/dL and was markedly reduced by lomitapide to a nadir of 176.7 +/- 46.3mg/dL (58.4 +/- 6.8% decrease). Six patients achieved recommended target levels for children below 135mg/dL, five of whom had LA frequency reduced. In one case, LDL-C levels were close to target when lomitapide was started but remained stable despite 75% reduction in LA frequency (from twice weekly to biweekly). Adverse events were mainly gastrointestinal in nature, occurred early in the treatment course and were well managed. Three patients with excursions in liver function tests were managed chiefly without intervention; two patients had decreases in lomitapide dose.Conclusions Lomitapide demonstrated promising effectiveness in paediatric HoFH patients. Adverse events were manageable, and the clinical profile of the drug is apparently similar to that in adult patients.Funding Amryt Pharma.