The Long-Term Efficacy and Safety of Evinacumab in Pediatric Patients with Homozygous Familial Hypercholesterolemia.

Regeneron Pharmaceuticals, Inc. Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder caused primarily by mutations in the low-density lipoprotein (LDL) receptor gene and characterized by severely elevated levels of LDL cholesterol (LDL-C), leading to early-onset atherosclerotic cardiovascular disease. Currently, few treatments are available to lower LDL-C levels in pediatric patients with HoFH. In Part B of a three-part open-label study (NCT04233918), the addition of evinacumab, an angiopoietin-like-3 inhibitor, to background lipid-lowering therapies (LLTs) reduced LDL-C from baseline to Week 24 by 48% in patients with HoFH aged 5-11 years. Evaluate the long-term (up to 72 weeks) efficacy and safety of evinacumab in pediatric patients with HoFH. This open-label, three-part study enrolled patients aged 5-11 years with LDL-C >130 mg/dL on optimized LLT, including apheresis and lomitapide. Part A was a Phase 1b, single-dose, 16-week study including six patients who received intravenous (IV) evinacumab 15 mg/kg. Part B was a Phase 3, 24-week open-label treatment study including 14 patients who had not participated in Part A. Part C was a Phase 3, 48-week open-label extension study, with an optional 24-week follow-up period, which included all 20 patients from both Parts A and B. In Parts B and C, patients received IV evinacumab 15 mg/kg every 4 weeks. We report data pooled from Parts B and C that includes results from Part A patients who participated in Part C and had 48 weeks of evinacumab treatment, and Part B patients who participated in Parts B and C and had a total treatment duration of 72 weeks. All 20 patients completed Part C. Mean (standard deviation [SD]) LDL-C at baseline was 301.9 (149.1) mg/dL. Evinacumab reduced mean LDL-C by 44.6% (mean [SD] reduction of 131.1 [90.2] mg/dL) and 40.7% (mean [SD] reduction of 115.8 [101.2] mg/dL) from baseline to Weeks 48 (n=16) and 72 (n=14), respectively. Evinacumab reduced mean apolipoprotein B (Week 48: 38.3%; Week 72: 34.0%), non-high-density lipoprotein cholesterol (Week 48: 45.3%; Week 72: 41.6%), total cholesterol (Week 48: 44.7%; Week 72: 42.2%), and median lipoprotein(a) (Week 48: 17.3%; Week 72: 15.7%). Treatment-emergent adverse events (TEAEs) occurred in all 20 patients. Serious TEAEs occurred in two (10.0%) patients (tonsilitis [n=1]; aortic valve stenosis [n=1]), both were unrelated to the study drug. No treatment discontinuations or deaths were reported. In pediatric patients with HoFH, evinacumab demonstrated substantial and durable reductions in LDL-C and other atherogenic lipids, and was generally well tolerated. [ABSTRACT FROM AUTHOR]