Lomitapide for the treatment of paediatric patients with homozygous familial hypercholesterolaemia (APH-19) results from the efficacy phase of an open-label, multicentre, phase 3 study

Identifier:  imarina:9407094

Handle: https://hdl.handle.net/20.500.11797/imarina9407094

Authors:  Masana, L; Zambon, A; Schmitt, CP; Taylan, C; Driemeyer, J; Cohen, H; Buonuomo, PS; Alashwal, A; Al-Dubayee, M; Kholaif, N; Diaz-Diaz, JL; Maatouk, F; Martinez-Hervas, S; Mangal, B; Löwe, S; Cunningham, T

Abstract:
Background Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder characterised by extremely high concentrations of LDL cholesterol, leading to early-onset atherosclerosis. Lomitapide is an orally administered microsomal triglyceride transfer protein (MTP) inhibitor that effectively lowers LDL cholesterol and is approved for adults with HoFH. We aimed to investigate the efficacy and safety of lomitapide in paediatric patients with HoFH receiving standard-of-care lipid-lowering therapy. Methods APH-19 is an open-label, single-arm, phase 3 trial performed at 12 study centres in Germany, Israel, Italy, Saudi Arabia, Spain, and Tunisia. A 6-week run-in period was followed by a 24-week efficacy phase and an 80-week safety phase. Patients aged 5-17 years, on stable lipid-lowering therapy, with HoFH diagnosed using the criteria from the 2014 European Atherosclerosis Society Consensus Panel on HoFH were titrated to maximum tolerated doses of oral lomitapide, starting at 2 mg (patients aged 5-15 years) or 5 mg (patients aged 16-17 years). The primary endpoint was the percentage change from baseline to week 24 in LDL cholesterol, which was assessed in patients who had received at least one dose of lomitapide, and who had a baseline and at least one post-baseline measurement. The secondary outcomes were the percentage change from baseline at week 24 in total cholesterol, non-HDL cholesterol, VLDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04681170. Findings Between Dec 20, 2020, and Oct 16, 2022, 43 patients were included and treated (24 [56%] were female and 19 [44%] were male, and median age was 107 years [70-140]). Mean change from baseline in LDL cholesterol at week 24 was -535% (95% CI -616 to -454, p