Evinacumab in the treatment of homozygous familial hypercholesterolemia: data from real-world clinical practice and case report

Czech version

Authors: Vladimír Bláha
Authors‘ workplace: III. interní gerontometabolická klinika LF UK a FN Hradec Králové
Published in: AtheroRev 2025; 10(2): 111-115
Category: Reviews

Overview

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by biallelic mutations in genes regulating the activity of the low-density lipoprotein receptor. Patients with HoFH have significantly elevated LDL-cholesterol (LDL-C) concentrations and are at high risk of premature development of atherosclerotic cardiovascular disease despite combined lipid-lowering therapy. Evinacumab, a fully humanized monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3), represents a new therapeutic option. This article summarizes the mechanism of action, clinical evidence, and practical aspects of administering evinacumab in patients with HoFH based on data from real world evidence (RWE).

Keywords:

Cholesterol – evinacumab – data from real world evidence (RWE) – homozygous familial hypercholesterolemia

Sources

Cuchel M, Bruckert E, Ginsberg HN et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management.

A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014; 35(32): 2146–2157. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehu274>.

Kramer AI, Akioyamen LE, Lee S et al. Major adverse cardiovascular events in homozygous familial hypercholesterolaemia: a systematic review and meta-analysis. Eur J Prev Cardiol 2022; 29(5): 817–828. Dostupné z DOI: <http://dx.doi.org/10.1093/eurjpc/zwab224>.

Tromp TR, Hartgers ML, Hovingh GK et al. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet 2022; 399(10326): 719–728. Dostupné
z DOI: <http://dx.doi.org/10.1016/S0140–6736(21)02001–8>.

Ito MK, Watts GF. Challenges in the Diagnosis and Treatment of Homozygous Familial Hypercholesterolemia. Drugs 2015; 75(15): 1715–1724. Dostupné z DOI: <http://dx.doi.org/10.1007/s40265–015–0466-y>.

Stefanutti C. Lomitapide-a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia. Curr Atheroscler Rep 2020; 22(8): 38. Dostupné z DOI: <http://dx.doi.org/10.1007/s11883–020–00858–4>.

Watts GF, Gidding SS, Hegele RA et al. International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia. Nat Rev Cardiol 2023; 20(12): 845–869. Dostupné z DOI: <http://dx.doi.org/10.1038/s41569–023–00892–0>.

Thompson GR. The scientific basis and future of lipoprotein apheresis. Ther Apher Dial 2022; 26(1): 32–36. Dostupné z DOI: <http://dx.doi.org/10.1111/1744–9987.13716>.

Bajaj A, Cuchel M. Advancements in the treatment of homozygous familial hypercholesterolemia. J AtherosclerThromb 2022; 29(8): 1125–1135. Dostupné z DOI: <http://dx.doi.org/10.5551/jat.RV17065>.

Burks KH, Basu D, Goldberg IJ et al. Angiopoietin-like 3: an important protein in regulating lipoprotein levels. Best Pract Res Clin Endocrinol Metab 2023; 37(3): 101688. Dostupné z DOI: <http://dx.doi.org/10.1016/j.beem.2022.101688>.

Dewey FE, Gusarova V, Dunbar RL et al. Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease. New Engl J Med 2017; 377(3): 211–221. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1612790>.

Raal FJ, Rosenson RS, Reeskamp LF et al. Evinacumab for Homozygous Familial Hypercholesterolemia. N Engl J Med 2020; 383(8): 711–720. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2004215>.

Goldberg AC, Hopkins PN, Toth PP et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011; 5(3): 133–140. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2011.03.001>.

Raal FJ, Rosenson RS, Reeskamp LF et al. The Long-Term Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia. JACC Adv 2023; 2(9): 100648. Dostupné
z DOI: <http://dx.doi.org/10.1016/j.jacadv.2023.100648>.

Stefanutti C, Chan DC, Di Giacomo S et al. Long-Term Efficacy and Safety of Evinacumab in Patients with Homozygous Familial Hypercholesterolemia: Real-World Clinical Experience. Pharmaceuticals 2022; 15(11): 1389. Dostupné z DOI: <http://dx.doi.org/10.3390/ph15111389>.

Stefanutti C, Chan DC, Zeppa G et al. Real-world experience of long-term efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia treated and untreated with lipoprotein apheresis. J Clin Lipidol 2024; 18(5): e817-e824. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2024.05.006>.

Wilkinson MJ, Bijlani P, Davidson MH et al. Real-World Effectiveness and Safety of Evinacumab in Children and Adults With Homozygous Familial Hypercholesterolemia: A Multisite US Perspective. Arterioscler Thromb Vasc Biol 2025;45(7): 1310–1315. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.124.322364>.

Rosenson RS, Reeskamp LF, Kastelein JJP. The Efficacy and Safety of Evinacumab in Homozygous Familial Hypercholesterolemia Patients with Little to No Low-Density Lipoprotein Receptor Activity. J Clin Lipidol 2020; 14(4): 552. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2020.05.019>.

Béliard S, Saheb S, Litzler-Renault S et al. Evinacumab and Cardiovascular Outcome in Patients With Homozygous Familial Hypercholesterolemia. Arterioscler Thromb Vasc Biol 2024; 44(6): 1447–1454. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.123.320609>.

Gaudet D, Greber-Platzer S, Reeskamp LF et al. Evinacumab in homozygous familial hypercholesterolaemia: long-term safety and efficacy. Eur Heart J 2024; 45(27): 2422–2434. Dostupné
z DOI: <http://dx.doi.org/10.1093/eurheartj/ehae325>.