Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial

Abstract

Background and Lerodalcibep, a novel small recombinant fusion protein of a proprotein convertase subtilisin/kexin type 9 gene–binding do-Aims main (adnectin) and human serum albumin, demonstrated highly effective low-density lipoprotein cholesterol (LDL-C) reduction with monthly 300 mg in 1.2 mL subcutaneous dosing in Phase 2. In this global Phase 3 trial, the safety and efficacy of lerodalcibep were evaluated in heterozygous familial hypercholesterolaemia patients requiring additional LDL-C lowering. Methods Patients were randomized 2:1 to monthly subcutaneous injections of either lerodalcibep 300 mg or placebo for 24 weeks. The primary efficacy endpoints were the per cent change from baseline in LDL-C at Week 24 and the mean of Weeks 22 and 24. Results In 478 randomized subjects [mean age (range); 53 (18–80) years, 51.7% female, mean (SD) baseline LDL-C 3.88 (1.66) mmol/L], lerodalcibep reduced LDL-C, compared with placebo by an absolute amount of 2.08 (0.11) mmol/L [LS mean (SE); 95% confidence interval −2.30 to −1.87] with a percentage difference of −58.61 (3.25)% at Week 24 and by 2.28 (0.10) mmol/L (95% confidence interval −2.47 to −2.09) with a percentage difference of −65.0 (2.87)% at the mean of Weeks 22 and 24 (P