Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial
Makaleler > Tam Makale · 2023
Yazarlar: Frederick Raal, Nyda Fourie, Russell Scott, Dirk Blom, Matthys De Vries Basson, Latife Meral KAYIKÇIOĞLU, Kate Caldwell, David Kallend, Evan Stein, LIBerate-HeFH Investigators, Traci Turner, Jean Bergeron, Artuela Caku, Avishay Elis, Ronen Durst, Zafer Yalim, Latife Meral KAYIKÇIOĞLU, Bahadir Kirilmaz, Atac Celik, Irfan Duzen, Abdurraham Oguzhan, Ibrahim Basarici, Frederick Raal, Dirk Blom, Marc Abelson, Matthys Basson, Lesley Burgess, Nyda Fourie, Eli Heggen, Emil Asprusten, Vimal Mehta, Raman Puri, Ashwani Mehta, Preeti Gupta, Milan Chag, Akshyaya Pradhan, Francisco Fuentes Jimenez, Fernando Civeira Murillo, Xavier Pinto Sala, Russell Scott
European Heart Journal, Uluslararası, Wos, 2023, cilt 44, ss 4272-4280
DOI: 10.1093/eurheartj/ehad596
Özet
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.