Evinacumab and Cardiovascular Outcome in Patients With Homozygous Familial Hypercholesterolemia

BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) remain at very high cardiovascular risk despite the best standard of care lipid-lowering treatment. The addition of evinacumab, an angiopoietin-like protein 3 monoclonal antibody, more than halves low-density lipoprotein cholesterol in short-term studies. This study evaluated whether the evinacumab response was durable in the long term and improved cardiovascular outcome. METHODS: The OLE ELIPSE HoFH (Open-Label Extension to Evinacumab Lipid Studies in Patients With HoFH) study included newly diagnosed patients and those completing the ELIPSE HoFH trial, on stable lipid-lowering therapy including lipoprotein apheresis but not lomitapide. All patients received evinacumab (15 mg/kg intravenously) every 4 weeks, with no change in concomitant lipid-lowering treatment during the first 6 months. The primary efficacy end points were the mean absolute and percentage changes in low-density lipoprotein cholesterol from baseline to 6 months. A key secondary end point was cardiovascular event-free survival, which was compared with a control HoFH cohort not treated with evinacumab or lomitapide and matched for age, sex, and lipoprotein apheresis, derived from French Registry of Familial hypercholesterolemia. RESULTS: Twelve patients, 5 women and 7 men (12-57 years), were enrolled in 3 centers in France. At 6 months, the mean low-density lipoprotein cholesterol reduction with evinacumab was 3.7 mmol/L or 56% (from 6.5 mmol/L at baseline to 2.8 mmol/L; P<0.0001) and was sustained over the median 3.5-year follow-up. No patients on evinacumab experienced cardiovascular events versus 13 events for 5/21 (24%) over 4 years in the control cohort (likelihood P=0.0267). CONCLUSIONS: Real-life, long-term evinacumab adjunctive to lipid-lowering therapy including lipoprotein apheresis led to sustained low-density lipoprotein cholesterol lowering and improved cardiovascular event-free survival of patients with HoFH.