Key result
Evinacumab 15 mg/kg administered intravenously every 4 weeks reduced LDL-C by 41.3% to 77.3% in six children aged 1 to <5 years with homozygous familial hypercholesterolemia.
Why the study?
Evinacumab significantly reduces LDL-C in HoFH, but pharmacokinetic and efficacy analyses were needed in patients aged < 5 years.
Does evinacumab 15 mg/kg iv q4w reduce LDL-C in children aged < 5 years with homozygous familial hypercholesterolemia?
Does evinacumab 15 mg/kg iv q4w reduce LDL-C in children aged < 5 years with homozygous familial hypercholesterolemia?
Evinacumab 15 mg/kg iv every 4 weeks provides clinically meaningful LDL-C reductions in children aged < 5 years with homozygous familial hypercholesterolemia, consistent with pharmacokinetic modeling.
Model predictions may guide evinacumab dosing in <5-year-old HoFH patients; leaves open prospective validation before practice change.
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.
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Bihorel et al. (2025) studied Homozygous Familial Hypercholesterolemia (n=6). Evinacumab vs. Baseline was evaluated on Percent change from LDL-C baseline (% ∆LDL-C). Evinacumab 15 mg/kg administered intravenously every 4 weeks reduced LDL-C by 41.3% to 77.3% in six children aged 1 to <5 years with homozygous familial hypercholesterolemia.
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