Optimizing treatment in homozygous familial hypercholesterolemia: Monocentric observational clinical study on efficacy and safety of evinacumab and lomitapide combination.

Authors

Marta Biolo, Maria Giovanna Lupo, Giorgia Marodin, Camilla Portinari, Alberto Zambon, Sandra Bertocco, Lorenzo Previato, Paolo Simioni, Nicola Ferri, Sabina Zambon

Published in

Journal of clinical lipidology. Volume 20. Issue 6. Pages 1086-1096. Epub Mar 27, 2026.

Abstract

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.
We evaluated the efficacy and safety of this therapeutic combination in patients with HoFH.
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.
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.
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.

PMID:
42831593
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

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