Evinacumab promising treatment for pediatric patients with homozygous familial hypercholesterolemia suggests a new study published in the Circulation.Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDLR (LDL receptor) function. Given that severely elevated LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating a largely unmet need for aggressive LDLR-independent lipid-lowering therapies in young patients with HoFH. Here we present the first evaluation of the efficacy and safety of evinacumab, a novel LDLR-independent lipid-lowering therapy, in pediatric patients with HoFH from parts A and B of a 3-part study.

The phase 3, part B, open-label study treated 14 patients 5 to 11 years of age with genetically proven HoFH (true homozygotes and compound heterozygotes) with LDL-C >130 mg/dL, despite optimized lipid-lowering therapy (including LDLR-independent apheresis and lomitapide), with intravenous evinacumab 15 mg/kg every 4 weeks.
RESULTS:
Evinacumab treatment rapidly and durably (through week 24) decreased LDL-C with profound reduction in the first week, with a mean (SE) LDL-C reduction of −48.3% (10.4%) from baseline to week 24. ApoB (mean [SE], –41.3% [9.0%]), non–high-density lipoprotein cholesterol (–48.9% [9.8%]), and total cholesterol (–49.1% [8.1%]) were similarly decreased. Treatment-emergent adverse events were reported in 10 (71.4%) patients; however, only 2 (14.3%) reported events were considered to be treatment-related (nausea and abdominal pain). One serious treatment-emergent adverse event of tonsillitis occurred (n=1), but this was not considered treatment-related.
Evinacumab constitutes a new treatment for pediatric patients with HoFH and inadequately controlled LDL-C despite optimized lipid-lowering therapy, lowering LDL-C levels by nearly half in these extremely high-risk and difficult-to-treat individuals.
Reference:
Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia
Albert Wiegman, Susanne Greber-Platzer, Shazia Ali, M. Doortje Reijman, Eliot A Brinton, Min-Ji Charng, Shubha Srinivasan, Carissa Baker-Smith, Seth Baum, Julie A. Brothers, Jacob Hartz, Patrick M. Moriarty, Jeanne Mendell, Sébastien Bihorel, Poulabi Banerjee, Richard T. George, Boaz Hirshberg and Robert Pordy
Originally published20 Oct 2023https://doi.org/10.1161/CIRCULATIONAHA.123.065529Circulation. 2023;0
Keywords:
Evinacumab, promising, treatment, pediatric, patients, homozygous, familial, hypercholesterolemia, Min-Ji Charng, Shubha Srinivasan, Carissa Baker-Smith, Seth Baum, Julie A. Brothers, Jacob Hartz, Patrick M. Moriarty, Jeanne Mendell, Sébastien Bihorel, Poulabi Banerjee