Document Type

Article

Publication Date

11-2025

Identifier

DOI: 10.1002/psp4.70017; PMCID: PMC12625149

Abstract

Evinacumab, an angiopoietin-like 3 inhibitor, significantly reduces low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). Herein, we report pharmacokinetic and efficacy analyses of evinacumab in <  5-year-old patients with HoFH. Population pharmacometric models characterizing evinacumab exposure and LDL-C response accounting for lipoprotein apheresis effect in ≥ 5-year-old patients were adapted for growth and maturation to predict and compare evinacumab and LDL-C concentrations across age/weight groups in virtual ≥ 6-month-old patients receiving 15 mg/kg evinacumab intravenous (iv) infusions every 4 weeks (q4w). As expected from allometric theory, weight-based dosing resulted in decreasing evinacumab exposures with declining body weight. Consistent with trends observed in > 5-year-old patients, the predicted percent change from LDL-C baseline (%∆LDL-C) was generally comparable or even higher in <  5-year-old patients (63.0%-68.5%) than in 5- to <  18-year-old patients (61.3%-67.8%) or adults (51.7%), with the predicted percentages of patients achieving %∆LDL-C > 50% also higher in <  5-year-old patients (82.0%-86.9%) versus 5- to <  18-year-old patients (72.0%-84.5%) and adults (54.8%). Through a managed access program, six 1- to <  5-year-old patients received between 5 and 23 iv infusions of 15 mg/kg evinacumab q4w. Rapid and clinically meaningful LDL-C reductions were observed, with %∆LDL-C at the last reported dose ranging from 41.3% to 77.3%. Based on the actual patient dosing and plasmapheresis history, model-predicted evinacumab and LDL-C concentrations were comparable to the observed data collected in the managed access program. Overall, this analysis provides evidence for the use of evinacumab 15 mg/kg iv q4w dosing regimen in 6-month-old to 5-year-old patients.

Journal Title

CPT Pharmacometrics Syst Pharmacol

Volume

14

Issue

11

First Page

1835

Last Page

1847

MeSH Keywords

Humans; Hyperlipoproteinemia Type II; Child, Preschool; Cholesterol, LDL; Male; Female; Infant; Antibodies, Monoclonal; Models, Biological; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Treatment Outcome; Angiopoietin-Like Protein 3; Infusions, Intravenous; Body Weight

PubMed ID

40095766

Keywords

angiopoietin‐like 3; evinacumab; extrapolation; homozygous familial hypercholesterolemia; low‐density lipoprotein cholesterol; pediatric; pharmacodynamics; pharmacokinetics

Comments

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Publisher's Link: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/psp4.70017

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