Abstract 12756: Long-Term Efficacy and Safety of Evinacumab in Adult and Adolescent Patients With Homozygous Familial Hypercholesterolemia

Introduction: Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare genetic lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease, underscoring the need for early and aggressive treatment. Evinacumab, an angiopoietin-like 3 inhibitor, significantly reduced LDL-C in patients with HoFH in a pivotal Phase 3 trial (NCT03399786). The current study assesses long-term safety and efficacy of evinacumab in patients with HoFH. Methods: This is an interim analysis of an evinacumab open-label Phase 3 trial (NCT03409744) in adult and adolescent(12-<18 years) patients with HoFH. Patients who previously received evinacumab or who were evinacumab-naïve both received intravenous evinacumab 15 mg/kg every 4 weeks. Results: A total of 115 patients (50.4% male; mean [range] age 39 [12-75] years; 11.3% adolescent) were enrolled and treated for a mean (range) duration of 53 (4-132) weeks. At baseline, mean (standard deviation [SD]) LDL-C was 261.8 (160.5) mg/dL; 44 (38.3%) patients were receiving concomitant lipoprotein apheresis. At Week 24, data were available for 81 patients. From baseline to Week 24, evinacumab reduced mean LDL-C for all patients by 43.7% (mean [SD], 133.0 [125.9] mg/dL); mean LDL-C reduction for adult (n=72) and adolescent (n=9) subgroups was 42.6% (mean [SD], 126.7 [127.9] mg/dL) and 52.4% (mean [SD], 183.4 [101.6] mg/dL), respectively. Treatment-emergent adverse events (TEAEs) occurred in 76 (66.1%) patients; one patient reported pregnancy which led to discontinuation of study treatment per protocol. Serious TEAEs were reported by 16 (13.9%) patients; two (1.7%) patients experienced a TEAE resulting in death, none of which were considered related to study treatment. Conclusions: In this large cohort of patients with HoFH, evinacumab markedly reduced LDL-C irrespective of age. Evinacumab was generally well tolerated, and the efficacy and safety of evinacumab was sustained over the long term.