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. 2023 Oct 21;44(40):4272-4280.
doi: 10.1093/eurheartj/ehad596.

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

Collaborators, Affiliations

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

Frederick Raal et al. Eur Heart J. .

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.

Keywords: Familial hypercholesterolaemia; Lerodalcibep; Low-density lipoprotein cholesterol.

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Figures

Structured Graphical Abstract
Structured Graphical Abstract
Lerodalcibep, a novel anti-proprotein convertase subtilisin/kexin type 9 gene small binding protein for the management of heterozygous familial hypercholesterolaemia. ASCVD, atherosclerotic cardiovascular disease; ESC, European Society of Cardiology; FH, familial hypercholesterolaemia; ITT, intention to treat; LDL-C, low-density lipoprotein cholesterol; SC, subcutaneous.
Figure 1
Figure 1
Low-density lipoprotein cholesterol (Friedewald) at each visit—intention-to-treat population; absolute reduction in mmol/L (A) and placebo adjusted per cent reduction (B)
Figure 2
Figure 2
Forest plot showing low-density lipoprotein cholesterol reduction with lerodalcibep in different subgroups. BMI, body mass index; IRT, interactive response technology
Figure 3
Figure 3
Percentage of patients achieving a ≥50% reduction in low-density lipoprotein cholesterol and European Society of Cardiology–recommended low-density lipoprotein cholesterol targets with lerodalcibep compared with placebo during the study

References

    1. Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide prevalence of familial hypercholesterolemia: meta-analyses of 11 million subjects. J Am Coll Cardiol 2020;75:2553–66. 10.1016/j.jacc.2020.03.057 - DOI - PubMed
    1. EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC) . Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Lancet 2021;398:1713–25. 10.1016/S0140-6736(21)01122-3 - DOI - PubMed
    1. Berberich AJ, Hegele RA. The complex molecular genetics of familial hypercholesterolaemia. Nat Rev Cardiol 2019;16:9–20. 10.1038/s41569-018-0052-6 - DOI - PubMed
    1. Luirink IK, Wiegman A, Kusters DM, Hof MH, Groothoff JW, de Groot E, et al. . 20-year follow-up of statins in children with familial hypercholesterolemia. N Engl J Med 2019;381:1547–56. 10.1056/NEJMoa1816454 - DOI - PubMed
    1. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. . 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111–88. 10.1093/eurheartj/ehz455 - DOI - PubMed

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