Physicians' Academy for Cardiovascular Education

PCSK9 inhibitor also effective and safe in children with HoFH?

Efficacy and safety of alirocumab in children and adolescents 2 with homozygous familial hypercholesterolemia: phase 3, 3 multinational open-label study

Literature - Bruckert E, Caprio S, Wiegman A, et al. - Arterioscler Thromb Vasc Biol. 2022;42:1447-57. doi: 10.1161/ATVBAHA.122.317793.

Introduction and methods


Despite advances in the treatment of patients with homozygous familial hypercholesterolemia (HoFH), most patients do not achieve target LDL-c levels with current lipid-modifying therapy [1]. Alirocumab is a human monoclonal antibody that selectively binds to PCSK9, a protein that plays a role in lipid homeostasis [2]. Alirocumab is indicated as an adjunct to diet in adults with primary hypercholesterolemia or mixed dyslipidemia, and for secondary prevention in established atherosclerotic CVD in adults [3,4]. However, this PCSK9 inhibitor is not approved for use in the pediatric population.

Aim of the study

This study examined the efficacy and safety of alirocumab in children with inadequately controlled HoFH.


The researchers conducted an international, multicenter, open-label, single-arm, phase 3 study in which 18 patients aged 8-17 years with HoFH received a subcutaneous injection of alirocumab 75 mg (body weight <50 kg) or 150 mg (body weight ≥50 kg) every 2 weeks for up to 48 weeks, in addition to background therapy, after a run-in period (≤4 weeks) and a screening period (≤2 weeks). Patients were eligible to participate if their disease was inadequately controlled despite optimal therapy with a statin and/or other lipid-modifying drugs at stable dose for ≥4 weeks. Patients with a null/null genotype for LDLR were excluded.


The primary outcome was the percent change in LDL-c levels from baseline to week 12. Secondary outcomes were: (a) the percent change in LDL-c levels from baseline to weeks 24 and 48; (b) the percent change in HDL-c, non-HDL-c, total cholesterol, triglyceride, apolipoprotein (Apo) A1 and B and lipoprotein a (Lp(a)) levels from baseline to weeks 12, 24 and 48; (c) the percentage of patients in whom LDL-c levels had decreased by ≥15% at weeks 12, 24 and 48; and (d) the absolute change in LDL-c levels from baseline to weeks 12, 24 and 48. Changes were expressed as least square mean. In addition, the safety of alirocumab was assessed.

Main results


Other lipid parameters



The results of this international, multicenter, open-label, phase 3 study suggest that subcutaneous injection of alirocumab every 2 weeks for up to 48 weeks is effective and safe in addition to other lipid-modifying therapy in children with inadequately controlled HoFH. There was heterogeneity in the response to alirocumab in lowering LDL-c, and the authors therefore highlight the importance of measuring LDL-receptor activity in addition to the genotype determination to decide on treatment strategies.


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Find this article online at Arterioscler Thromb Vasc Bio.

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