P4A047: Efficacy and Safety of Evinacumab in Pediatric Patients with Homozygous Familial Hypercholesterolemia

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder predominantly caused by mutations in the low-density lipoprotein (LDL) receptor gene, which is characterized by severely elevated LDL cholesterol (LDL-C) levels, beginning in utero. Although cardiovascular events often occur during childhood and adolescence, few treatments effectively lower LDL-C in pediatric patients with HoFH. We report the efficacy and safety of evinacumab, a monoclonal antibody inhibitor of angiopoietin-like 3, in these patients.

Methods: This open-label, three-part study (NCT04233918) enrolled 14 patients 5–11 years old with LDL-C >130 mg/dL on optimized lipid-lowering therapy, including apheresis. Part B, reported here, consisted of: ≤8-week run-in, a 1–2-week screening period, and a 24-week open-label treatment period. All patients in Part B received intravenous evinacumab 15 mg/kg every 4 weeks. The primary endpoint was mean change in LDL-C.

Results: All patients completed Part B. At Part B baseline, mean (standard deviation [SD]) age was 9.1 (1.9) years and mean (SD) LDL-C was 263.7 (91.0) mg/dL. At week 24, mean change in LDL-C from baseline was –48.3% (standard error [SE]: 10.4%). Mean (SE) changes 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. Treatment-emergent adverse events (TEAEs) occurred in 10 (71.4%) patients, but were considered treatment-related only in two (14.3%) patients (nausea and abdominal pain; both ongoing). No treatment discontinuations due to TEAEs or deaths were reported. A serious TEAE of tonsilitis occurred in one patient but was not considered treatment-related.

Conclusion: In children with HoFH and inadequately controlled LDL-C despite pre-existing treatment (including apheresis and lomitapide), evinacumab effectively lowers LDL-C and other atherogenic lipid levels by an additional 40–50%. Evinacumab is generally well tolerated.