Abstract 16672: Effects of Evinacumab on Atherogenic Lipoproteins in Children and Adolescents From Ages 5 to 17 Years With Homozygous Familial Hypercholesterolemia

Abstract

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by severely elevated LDL-C levels from birth. Diagnosis and aggressive LDL-lowering treatment (LLT) before adulthood are essential for optimal ASCVD prevention in HoFH; however, it is often undiagnosed and undertreated in pediatric patients. Specifically, HoFH children and adolescents routinely require advanced LLT, since few achieve LDL-C goal on standard LLT. Evinacumab, a novel angiopoietin-like-3 inhibitor and advanced LLT, has an established safety profile in younger and older pediatric HoFH patients, 5-11 and 12-17 years, respectively. For the first time, we compare its lipid efficacy in these two groups. Methods: Fourteen patients ages 5-11 years (Study 17100 part B; NCT04233918) and 14 patients ages 12-17 years (Study 1719; NCT03409744), all with HoFH on stable LLT, were treated with IV evinacumab 15 mg/kg Q4W. Notably, in Study 17100 part B, no patients were taking PCSK9 inhibitors at study entry, while in Study 1719, 42.9% of patients were receiving a PCSK9 inhibitor at baseline. Apheresis use differed little, 50.0% in the younger study vs 64.3% in the older. LDL-C and other atherogenic lipoproteins were tested at baseline and 24 weeks. Results: In patients ages 5-11 years, mean (SD) baseline LDL-C was 263.7 (91.0) mg/dL and was lowered 48.3% (131.9 mg/dL) by evinacumab ( Table ). In patients ages 12-17 years, baseline LDL-C was 300.4 (100.5) mg/dL and was lowered 55.4% (180.5 mg/dL), with similar baseline and changes to those of the younger patients. In both groups, evinacumab markedly reduced ApoB, non-HDL-C, and Lp(a) ( Table ). Conclusions: Evinacumab strikingly and comparably reduces atherogenic lipids in younger and older pediatric HoFH patients. Since standard LLT rarely lowers LDL-C levels to treatment goals in pediatric HoFH, evinacumab should be strongly and urgently considered in these patients whenever further LDL-lowering is needed after optimizing standard LLT.