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Clinical Trial
. 2025 May;42(5):2465-2479.
doi: 10.1007/s12325-025-03160-4. Epub 2025 Apr 2.

Evinacumab for Homozygous Familial Hypercholesterolemia: The Italian Cohort of the ELIPSE HoFH Study

Gabriella Iannuzzo #  1 , Ilenia Calcaterra #  2 , Marco Gentile  3 , Claudia Stanzione  2 , Francesca De Ruberto  2 , Maria Donata Di Taranto  3 , Giuliana Fortunato  3 , Matteo Di Minno  2
Affiliations
Clinical Trial

Evinacumab for Homozygous Familial Hypercholesterolemia: The Italian Cohort of the ELIPSE HoFH Study

Gabriella Iannuzzo et al. Adv Ther. 2025 May.

Abstract

Introduction: Homozygous familial hypercholesterolemia (HoFH) is a severe rare genetic disorder characterized by elevated plasma low-density lipoprotein (LDL) cholesterol levels. Here, we report data from the Italian cohort of the Evinacumab Lipid Studies in Patients with Homozygous Familial Hypercholesterolemia (ELIPSE HoFH) trial.

Methods: ELIPSE HoFH was conducted at 30 sites in 11 countries, with 2-10 patients enrolled per country. The study included patients aged ≥ 12 years with LDL cholesterol ≥ 70 mg/dl (1.8 mmol per liter) at screening despite stable maximally tolerated lipid-lowering therapy. Patients were randomly assigned evinacumab (15 mg/kg every 4 weeks) or matching placebo for 24 weeks, with an option for a 24-week open-label extension or follow-up period thereafter. The Italian cohort included seven patients assigned to evinacumab.

Results: Five patients (3 males and 2 females) received evinacumab and were included in this report. Substantial and consistent reductions in LDL cholesterol from baseline levels were observed in all patients at all follow-up time points. Overall, an 84.5% decrease in median (range) LDL cholesterol was observed, from 323 (203-587) mg/dl in 2016 to 50.0 (13-103) mg/dl (P = 0.043) in 2019, with LDL cholesterol levels stable through 2023. Total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, and triglycerides decreased markedly over time. Evinacumab was well tolerated, with no treatment-related adverse events reported.

Conclusion: Evinacumab substantially lowered LDL cholesterol levels in patients with HoFH regardless of the degree of LDL receptor function, with low levels sustained over 5 years of follow-up.

Trial registration: ClinicalTrials.gov identifier NCT03399786 registered 16 January 2018.

Keywords: Angiopoietin-like 3 protein; ELIPSE HoFH; Evinacumab; Homozygous familial hypercholesterolemia; LDL cholesterol; Triglycerides.

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Conflict of interest statement

Declarations. Conflict of Interest: Gabriella Iannuzzo, Ilenia Calcaterra, Marco Gentile, Claudia Stanzione, Francesca de Ruberto, Maria Donata di Taranto, Giuliana Fortunato and Matteo Di Minno have nothing to disclose. Ethical Approval: The protocol for ELIPSE HoFH was approved by the relevant institutional review boards or ethics committees (Federico II University Ethics Committee under number 358/18/ESIB8 and compassionate use by the same committee under numbers 379/21, 380/21, 381/21, 382/21, 383/21,384/21, 385/21). The trial was conducted in accordance with the Declaration of Helsinki and its amendments and Good Clinical Practice guidelines. Written informed consent was obtained from each patient.

Figures

Fig. 1
Fig. 1
Individual changes in low-density lipoprotein (LDL) cholesterol over time (N = 5)
Fig. 2
Fig. 2
Percent change from baseline levels of median low-density lipoprotein (LDL) cholesterol over time (N = 5)
Fig. 3
Fig. 3
Percent change from baseline levels of mean low-density lipoprotein (LDL) cholesterol over time (N = 5)
See this image and copyright information in PMC

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