Evinacumab Markedly Reduces Low-density Lipoprotein Cholesterol in Adolescent Patients With Homozygous Familial Hypercholesterolemia†

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Lead Author's Financial Disclosures Nothing to disclose. Study Funding Regeneron Pharmaceuticals, Inc. Background/Synopsis Homozygous familial hypercholesterolemia (HoFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease, underscoring the need for early and aggressive treatment. Evinacumab, an angiopoietin-like protein 3 inhibitor, is an effective LDL-C lowering drug in adult HoFH patients. Objective/Purpose The primary objective of the study is to evaluate the safety and tolerability of intravenous evinacumab 15 mg/kg every 4 weeks in adolescent patients with HoFH. Methods This is an interim analysis of an evinacumab open-label phase 3 trial (NCT03409ba744) in adolescent patients (aged 12 to <18 years) with HoFH. Patients who participated in a previous study (NCT03399786) or who were evinacumab-naive received intravenous evinacumab 15 mg/kg every 4 weeks. All patients were genotyped. Results In total, 13 patients (8 male; mean [range] age 14 [12-17] years) were treated for a mean (range) duration of 34.5 (4-61) weeks. At baseline, mean (standard deviation [SD]) LDL-C was 310.3 [97.3] mg/dL; 8 patients (61.5%) received lipoprotein apheresis. Treatment-emergent adverse events (TEAEs) occurred in 6 (46.2%) patients; no TEAEs were reported in more than 1 patient. One patient reported 2 serious adverse events, both considered unrelated to study drug. LDL-C data were available for 9 patients at week 24. Overall, evinacumab reduced mean LDL-C by 52.4% (mean [SD], 183.4 [101.6] mg/dL; Figure) from baseline to week 24. In patients with null-null (n=4) and non-null (n=5) LDL-receptor variants, evinacumab reduced mean LDL-C levels by 67.2% and 40.6%, respectively. Conclusions In this small sample of adolescent patients with HoFH, evinacumab markedly reduced LDL-C irrespective of genotype or background treatment in patients with HoFH. Evinacumab was generally well-tolerated with few TEAEs. Nothing to disclose.