Journal Article Ahead of print
PubMed: 41671678 DOI: 10.1016/j.atherosclerosis.2026.120657
Efficacy of evinacumab by genotype and low-density lipoprotein receptor function in patients with homozygous familial hypercholesterolaemia: A subanalysis from the ELIPSE open-label extension study.
Atherosclerosis 414:120657
Authors: Frederick J Raal, Susanne Greber-Platzer, Laurens F Reeskamp, Gabriella Iannuzzo, Robert S Rosenson, Samir Saheb, Claudia Stefanutti, Erik Stroes, Eric Bruckert, Alpana Waldron, Poulabi Banerjee, Robert Pordy, Pinay Kainth, Richard Jones, Daniel Gaudet
Affiliations
- Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology, Allergology and Endocrinology, Medical University of Vienna, Vienna, Austria.
- Department of Vascular Medicine, Amsterdam University Medical Center, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
- Department of Clinical Medicine and Surgery, University of Naples, Naples, Italy.
- Metabolism and Lipids Program, Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- LDL-apheresis Unit, Department of Endocrinology, Hôpital de la Pitié-Salpêtrière, Université Paris Diderot, Sorbonne Paris, Paris, France.
- Extracorporeal Therapeutic Techniques Unit, Lipid Clinic and Atherosclerosis Prevention Centre, Regional Centre for Rare Diseases, Immunohematology and Transfusion Medicine, Department of Molecular Medicine, Umberto I Hospital, 'Sapienza' University of Rome, Rome, Italy.
- Department of Endocrinology, Hôpital de la Pitié-Salpêtrière, Université Paris Diderot, Sorbonne Paris, Paris, France.
- Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA.
- Ultragenyx Pharmaceutical Inc, Novato, CA, USA.
- Clinical Lipidology and Rare Lipid Disorders Unit, Community Gene Medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21, Chicoutimi, Québec, Canada.
Abstract
BACKGROUND AND AIMS
Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder caused primarily by variants in both alleles of the gene encoding the low-density lipoprotein receptor (LDLR). This subanalysis of the ELIPSE open-label extension (OLE) study assessed the efficacy of evinacumab, an angiopoietin-like 3 inhibitor, by genotype and LDLR function in patients with HoFH.
METHODS
Patients aged ≥12 years with HoFH on stable lipid-lowering therapies received evinacumab 15 mg/kg intravenously every 4 weeks. Patients were grouped according to genotype: bi-allelic monogenic identical variants (true homozygous) or bi-allelic monogenic different LDLR variants (compound heterozygous); and by LDLR function: null/null variants resulting in <15% LDLR activity or negative/negative variants predicted to result in <2% LDLR activity.
RESULTS
One hundred and sixteen patients enrolled in the OLE. At baseline, 55 (47.4%) had either identical bi-allelic variants in LDLR (n = 53) or LDLRAP1 (n = 2), and 41 (35.3%) had different bi-allelic LDLR variants. Median (Q1, Q3) LDL-C levels were reduced by -53.8% (-42.6%, -67.0%) and -58.1% (-41.5%, -65.9%) by Week 8 of evinacumab treatment in the identical (LDLR or LDLRAP1) and different (LDLR) bi-allelic variant groups, respectively, and remained low at Week 104 (-50.9% [-34.9%, -60.3%] and -47.3% [-34.8%, -67.5%], respectively). At baseline, 36 (31.0%) patients had null/null LDLR variants, and 19 (16.4%) patients had negative/negative LDLR variants. Evinacumab treatment also resulted in rapid and sustained decreases in median LDL-C levels to Week 104 in these subgroups.
CONCLUSIONS
Evinacumab treatment resulted in sustained LDL-C reduction in patients with HoFH irrespective of genotype or LDLR function.
MeSH
Genes, Receptors, Ldl, Receptors, Lipoprotein, Lipoproteins, Arteriosclerosis, Genotype, Therapeutics, Lipoproteins, Ldl