Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia

• Published in: Circulation (New York, N.Y.) Vol. 149; no. 5; pp. 343 - 353
• Main Authors: Wiegman, Albert, Greber-Platzer, Susanne, Ali, Shazia, Reijman, M Doortje, Brinton, Eliot A, Charng, Min-Ji, Srinivasan, Shubha, Baker-Smith, Carissa, Baum, Seth, Brothers, Julie A, Hartz, Jacob, Moriarty, Patrick M, Mendell, Jeanne, Bihorel, Sébastien, Banerjee, Poulabi, George, Richard T, Hirshberg, Boaz, Pordy, Robert
• Format: Journal Article
• Language: English
• Published: United States 30.01.2024
• Subjects: Adolescent; Antibodies, Monoclonal; Anticholesteremic Agents - adverse effects; Child; Cholesterol, LDL - genetics; Homozygote; Homozygous Familial Hypercholesterolemia; Humans; Hyperlipoproteinemia Type II - diagnosis; Hyperlipoproteinemia Type II - drug therapy; Hyperlipoproteinemia Type II - genetics; atherosclerosis; lipids; homozygous familial hypercholesterolemia; lipoprotein; pediatrics; angiopoietin-like protein 3; evinacumab
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.123.065529

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDL receptor (LDLR) 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. 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 that 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. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04233918.