Optimizing Treatment in Homozygous Familial Hypercholesterolemia: Monocentric Observational Clinical Study on Efficacy and Safety of Evinacumab and Lomitapide Combination

BACKGROUND Genetic variants of the low-density lipoprotein (LDL) receptor cause homozygous familial hypercholesterolemia (HoFH). Disease-specific treatment options include lipoprotein apheresis and lomitapide, and more recently, the angiopoietin-like 3 (ANGPTL3)-targeting monoclonal antibody evinacumab. OBJECTIVE We evaluated the efficacy and safety of this therapeutic combination in patients with HoFH. METHODS We report a single-center, real-world clinical experience including 6 patients with HoFH, 4 of whom were pediatric, with persistently elevated LDL-cholesterol (LDL-C) (>130 mg/dL), despite optimized lipid-lowering therapy, including lipoprotein apheresis and lomitapide. These patients received intravenous evinacumab at 15 mg/kg every 4 weeks on top of stable background lipid-lowering therapy, including lomitapide, and after discontinuation of lipoprotein apheresis. RESULTS At baseline, immediately before evinacumab initiation, mean LDL-C was 289.6 ± 80.6 mg/dL (7.25 ± 2.08 mmol/L). Treatment with evinacumab resulted in a sustained reduction in LDL-C by 55.0% ± 12.5% through week 48. In addition, evinacumab reduced apolipoprotein B (ApoB) by 46.0% ± 10.5%, total cholesterol by 53.1% ± 11.4%, and triglycerides by 51.9% ± 8.2%. Plasma ANGPTL3 levels approximately doubled, whereas proprotein convertase subtilisin/kexin type 9 decreased modestly, reaching a −15% at week 24. The combination of evinacumab and lomitapide was generally well tolerated throughout the study period with no serious treatment-emergent adverse events. One patient experienced a delayed infusion reaction, and another a transient headache and flu-like symptoms. CONCLUSION Evinacumab added to lomitapide-based background lipid-lowering therapy was associated with marked reductions in LDL-C, ApoB, and other lipid parameters, with a favorable safety profile. These findings support the potential clinical usefulness of the evinacumab/lomitapide combination in both pediatric and adult patients with HoFH, although decisions regarding lipoprotein apheresis should remain individualized.