THE IMPACT OF EVINACUMAB THERAPY ON PEDIATRIC PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: RESULTS FROM PART B OF A PHASE 3 TRIAL

Abstract

Therapeutic Area: ASCVD /CVD Risk Reduction Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels. Currently, few treatments effectively lower LDL-C levels in pediatric patients with HoFH. Here, we report the efficacy and safety of evinacumab, a monoclonal antibody inhibitor of angiopoietin-like 3, in pediatric patients with HoFH. Methods: This is a three-part, open-label study (NCT04233918); Part B results are reported here. Part B enrolled 14 patients with HoFH 5–11 years old with LDL-C >130 mg/dL on optimized lipid-lowering therapy, including apheresis and lomitapide. All patients received intravenous evinacumab 15 mg/kg every 4 weeks. Results: All 14 patients completed Part B. Evinacumab treatment reduced mean (standard deviation) LDL-C from 263.7 (91.0) mg/dL at baseline to 131.8 (109.8) mg/dL at Week 24, with a mean (standard error [SE]) percent reduction of −48.3% (10.4%). Mean (SE) reductions in apolipoprotein B (−41.3% [9.0%]), non-high-density lipoprotein cholesterol (−48.9% [9.8%]), and total cholesterol (−49.1% [8.1%]) were also observed. Furthermore, percent LDL-C reduction observed at Week 24 from baseline based on the baseline LDL-C values or the presence of lomitapide treatment are presented in a Table. Additionally, the percent change from baseline in Lp(a) at Week 24 according to baseline apheresis status (Yes vs No) was similar: −43.7% (1.6%) versus −32.7% (1.4%), respectively. Treatment-emergent adverse events (TEAEs) occurred in 10 (71.4%) patients; no deaths or treatment discontinuations due to TEAEs were reported. Conclusions: Evinacumab substantially reduced LDL-C levels and other key atherogenic lipid parameters in pediatric patients with HoFH additive to any pre-existing treatment (including apheresis and lomitapide). Evinacumab was generally well-tolerated.