Evinacumab in patients aged 5–17 years with homozygous familial hypercholesterolemia

BACKGROUND AND AIMS Children and adolescents with homozygous familial hypercholesterolemia (HoFH) routinely require advanced lipid-lowering therapies (LLTs). We assess the long-term efficacy and safety of evinacumab, a novel LLT, in children and adolescents with HoFH. METHODS Study 17100 (NCT04233918) was a phase 3, single-arm, open-label study enrolling 20 children aged 5-11 years with HoFH. ELIPSE-OLE (NCT03409744) was a phase 3, single-arm study enrolling 14 adolescents aged 12-17 years with HoFH. Participants received intravenous evinacumab 15 mg/kg every 4 weeks; all individuals received stable LLT and most received lipoprotein apheresis (60 % of children aged 5-11 years; 64 % of adolescents aged 12-17 years). Outcomes included change from baseline to weeks 48 and 72 in low-density lipoprotein cholesterol (LDL-C) and other lipid parameters. Safety was assessed as treatment-emergent adverse events (TEAEs). RESULTS In children aged 5-11 years, mean (standard deviation SD) baseline LDL-C (301.9 149.1 mg/dL) was lowered by 45 % (131.1 mg/dL) at week 48 and 41 % (115.8 mg/dL) at week 72. In adolescents aged 12-17 years, mean (SD) baseline LDL-C (300.4 100.5 mg/dL) was lowered by 48 % (156.4 mg/dL) at week 48 and 51 % (165.6 mg/dL) at week 72. TEAEs occurred in 100 % and 86 % of participants aged 5-11 and 12-17 years, respectively. TEAEs were considered treatment related in four individuals aged 5-11 years (20 %); no one aged 12-17 years had treatment-related TEAEs (0 %). CONCLUSIONS Evinacumab markedly reduced LDL-C in children and adolescents with HoFH, beyond optimized standard LLT and lipoprotein apheresis. LDL-C remains above goal in most pediatric patients with HoFH, and evinacumab should be routinely considered whenever further LDL-C lowering is needed.