Abstract 13950: Real-World Effectiveness and Safety of Evinacumab in Pediatric and Adult Patients With Homozygous Familial Hypercholesterolemia: A Multi-Site US Perspective

Abstract

Introduction: Homozygous familial hypercholesterolemia (HoFH) is an autosomal co-dominant disorder characterized by extreme elevations in LDL-C and early onset ASCVD. Unfortunately, patients with HoFH generally experience poor LDL-C lowering with standard lipid-lowering therapy and rarely achieve LDL-C goals. Evinacumab is a monoclonal antibody administered by monthly IV infusion that binds angiopoietin-like 3 and when added to standard lipid-lowering therapies lowers LDL-C by ~50% in clinical trials involving patients with HoFH. Real-world effectiveness and safety of evinacumab is unknown. Methods: We performed retrospective chart review to assess effectiveness and safety of evinacumab in patients with HoFH in clinical practice at six US academic medical centers. The primary efficacy endpoint was the percent change in LDL-C from baseline to first follow-up and to most recent follow-up after evinacumab initiation. Secondary efficacy endpoints were percent change in non-HDL-C, triglycerides, total cholesterol, HDL-C, and achievement of an LDL-C <70 mg/dL. Adverse events were recorded. Results: Twenty-four patients (mean age 38 yrs; range 5-75) with HoFH were followed for a median of 63 weeks. Fifty percent were female, 66.7% had ASCVD, 87.5% were on a statin, 83.3% on ezetimibe, 66.7% on a PCSK9i, 24% on lomitapide, and 33.3% were undergoing lipoprotein apheresis. Significant reductions in LDL-C, non-HDL-C, total cholesterol, triglycerides, and HDL-C were observed both at first follow-up (4 weeks) and most recent follow-up (63 weeks) (p < 0.001 for all) (Table). Significantly more patients achieved LDL-C <70 mg/dL after evinacumab was added. No serious adverse events occurred and evinacumab was generally well-tolerated. Conclusions: Across six US academic medical centers, evinacumab was generally well-tolerated by patients with HoFH and lowered LDL-C by ~50%, consistent with results from clinical trials.