TY - JOUR
T1 - Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia
T2 - Phase 3, Multinational Open-Label Study
AU - Bruckert, Eric
AU - Caprio, Sonia
AU - Wiegman, Albert
AU - Charng, Min-Ji
AU - Zárate-Morales, C. zar A.
AU - Baccara-Dinet, Marie T.
AU - Manvelian, Garen
AU - Ourliac, Anne
AU - Scemama, Michel
AU - Daniels, Stephen R.
N1 - Funding Information: Acknowledgments We want to thank the children and adolescents and their families, as well as the investigators and their teams for participating in the study. We would also like to thank Dr J.C. Defesche for his invaluable contribution to the patient genotyping analyses. Medical writing and editorial assistance was provided by Alex van der Wateren, PhD, and Heather Shawcross, PhD, of Fishawack Communications Ltd, and was funded by Sanofi. We thank Wanda Stipek, PharmD, BCPS (Sanofi), for coordinating the development, facilitating author discussions, and critical review of this article. Sources of Funding This study was funded by Sanofi. Funding Information: We want to thank the children and adolescents and their families, as well as the investigators and their teams for participating in the study. We would also like to thank Dr J.C. Defesche for his invaluable contribution to the patient genotyping analyses. Medical writing and editorial assistance was provided by Alex van der Wateren, PhD, and Heather Shawcross, PhD, of Fishawack Communications Ltd, and was funded by Sanofi. We thank Wanda Stipek, PharmD, BCPS (Sanofi), for coordinating the development, facilitating author discussions, and critical review of this article. Publisher Copyright: © 2022 The Authors.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Background: Despite progress in treating homozygous familial hypercholesterolemia, most patients do not achieve low-density lipoprotein cholesterol (LDL-C) targets. This study examined efficacy and safety of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, alirocumab, in pediatric patients (aged 8-17 years) with inadequately controlled homozygous familial hypercholesterolemia. Methods: In this open-label, single-arm, multinational, Phase 3 study, patients (n=18) received alirocumab 75 mg or 150 mg (bodyweight <50 kg/≥50 kg) every 2 weeks as an adjunct to background treatment. The primary endpoint was percent change in LDL-C from baseline to Week 12. Secondary endpoints included changes in LDL-C and other lipid parameters up to 48 weeks, safety/tolerability, and alirocumab pharmacokinetics. Results: The mean age of patients was 12.4 years; 16/18 (89%) had mutations in the low-density lipoprotein receptor gene (LDLR) and 2/18 (11%) had mutations in the LDLR adapter protein 1 gene (LDLRAP1). At baseline, mean LDL-C (standard deviation) was 373.0 (193.5) mg/dL, which decreased by 4.1% at Week 12 (primary endpoint) and 11.4%, 13.2%, and 0.4% at Weeks 4, 24, and 48, respectively. At Week 12, 9/18 (50%) patients achieved LDL-C reductions ≥15%. Mean absolute LDL-C decreases ranged from 25 to 52 mg/dL over follow-up. A post hoc analysis demonstrated heterogeneity of responses according to genotype. There were no unexpected safety/tolerability findings. Free PCSK9 was reduced to near zero for all patients at Weeks 12 and 24. Conclusions: The study supports the efficacy and safety of alirocumab as a potential adjunct to treatment for some pediatric patients with homozygous familial hypercholesterolemia. Registration: URL: https://www.clinicaltrials.gov; NCT03510715.
AB - Background: Despite progress in treating homozygous familial hypercholesterolemia, most patients do not achieve low-density lipoprotein cholesterol (LDL-C) targets. This study examined efficacy and safety of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, alirocumab, in pediatric patients (aged 8-17 years) with inadequately controlled homozygous familial hypercholesterolemia. Methods: In this open-label, single-arm, multinational, Phase 3 study, patients (n=18) received alirocumab 75 mg or 150 mg (bodyweight <50 kg/≥50 kg) every 2 weeks as an adjunct to background treatment. The primary endpoint was percent change in LDL-C from baseline to Week 12. Secondary endpoints included changes in LDL-C and other lipid parameters up to 48 weeks, safety/tolerability, and alirocumab pharmacokinetics. Results: The mean age of patients was 12.4 years; 16/18 (89%) had mutations in the low-density lipoprotein receptor gene (LDLR) and 2/18 (11%) had mutations in the LDLR adapter protein 1 gene (LDLRAP1). At baseline, mean LDL-C (standard deviation) was 373.0 (193.5) mg/dL, which decreased by 4.1% at Week 12 (primary endpoint) and 11.4%, 13.2%, and 0.4% at Weeks 4, 24, and 48, respectively. At Week 12, 9/18 (50%) patients achieved LDL-C reductions ≥15%. Mean absolute LDL-C decreases ranged from 25 to 52 mg/dL over follow-up. A post hoc analysis demonstrated heterogeneity of responses according to genotype. There were no unexpected safety/tolerability findings. Free PCSK9 was reduced to near zero for all patients at Weeks 12 and 24. Conclusions: The study supports the efficacy and safety of alirocumab as a potential adjunct to treatment for some pediatric patients with homozygous familial hypercholesterolemia. Registration: URL: https://www.clinicaltrials.gov; NCT03510715.
UR - http://www.scopus.com/inward/record.url?scp=85142739570&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/ATVBAHA.122.317793
DO - https://doi.org/10.1161/ATVBAHA.122.317793
M3 - Article
C2 - 36325897
VL - 42
SP - 1447
EP - 1457
JO - Arteriosclerosis, thrombosis and vascular biology
JF - Arteriosclerosis, thrombosis and vascular biology
SN - 1079-5642
IS - 12
ER -