Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial
Frederick J. Raal, Nyda Fourie, Russell Scott, Dirk Blom, Matthys De Vries Basson, Meral Kayıkçıoğlu, Kate Caldwell, David Kallend, Evan A. Stein, LIBerate-HeFH Investigators, Traci Turner, Jean Bergeron, Artuela Çaku, Avishay Elis, Ronen Durst, Zafer Yalım, Meral Kayıkçıoğlu, Bahadır Kırılmaz, Ataç Çelik, Irfan Duzen, Abdurraham Oguzhan, İbrahim Başarıcı, Frederick J. Raal, Dirk Blom, M Abelson, Matthys M de V Basson, Lesley Burgess, Nyda Fourie, Eli Heggen, Emil Andreas Asprusten, Vimal Mehta, Raman Puri, Ashwani Mehta, Preeti Gupta, Milan Chag, Akshyaya Pradhan, Francisco Fuentes Jimenez, Fernando Civeira Murillo, Xavier Pinto Sala, Russell Scott
Abstract
BACKGROUND AND AIMS: Lerodalcibep, a novel small recombinant fusion protein of a proprotein convertase subtilisin/kexin type 9 gene-binding domain (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 < .0001 for all). With lerodalcibep, 68% of subjects achieved both a reduction in LDL-C ≥ 50% and the recommended European Society of Cardiology LDL-C targets during the study. Except for mild injection site reactions, treatment-emergent adverse events were similar between lerodalcibep and placebo. CONCLUSIONS: Lerodalcibep, a novel anti-proprotein convertase subtilisin/kexin type 9 gene small binding protein dosed monthly as an alternative to monoclonal antibodies, significantly reduced LDL-C in subjects with heterozygous familial hypercholesterolaemia with a safety profile similar to placebo.