Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia

• DOI: 10.1161/circulationaha.123.065529
• Publication Date: 2023-10-20T09:00:45Z
• Authors: Albert Wiegman; Susanne Greber-Pl...; 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; Robert Pordy
• Keywords: Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Adolescent; Original Research Articles; Anticholesteremic Agents; Homozygote; Humans; Antibodies, Monoclonal; Cholesterol, LDL; Child; 3. Good health

BACKGROUND: 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 LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating largely unmet need for aggressive LDLR-independent lipid-lowering therapies young patients with HoFH. Here we present the first evaluation of efficacy and safety evinacumab, novel therapy, pediatric HoFH from parts A B 3-part study. METHODS: The phase 3, part B, open-label study treated 14 5 11 years age genetically proven (true homozygotes compound heterozygotes) >130 mg/dL, despite optimized therapy (including apheresis lomitapide), intravenous evinacumab 15 mg/kg every 4 weeks. RESULTS: Evinacumab treatment rapidly durably (through week 24) decreased profound reduction week, mean (SE) −48.3% (10.4%) baseline 24. ApoB (mean [SE], –41.3% [9.0%]), non–high-density (–48.9% [9.8%]), total (–49.1% [8.1%]) were similarly decreased. Treatment-emergent adverse events reported 10 (71.4%) patients; however, only 2 (14.3%) considered be treatment-related (nausea abdominal pain). One serious treatment-emergent event tonsillitis occurred (n=1), but this was not treatment-related. CONCLUSIONS: constitutes new inadequately controlled lowering nearly half these extremely high-risk difficult-to-treat individuals. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04233918.