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Evinacumab for Homozygous Familial Hypercholesterolemia
Frederick J Raal1, Robert S Rosenson1, Laurens F Reeskamp1
1From the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg (F.J.R.); the Cardiometabolics Unit, Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York (R.S.R.), and Regeneron Pharmaceuticals, Tarrytown (S.A., P.B, K.-C.C., D.A.G., N.K., R.P., D.M.W. G.D.Y., Y.Z.) - both in New York; the Department of Vascular Medicine, University of Amsterdam, Amsterdam (L.F.R., G.K.H., J.J.P.K.); the Department of Internal Medicine and Surgery, Federico II University, Naples, Italy (P.R.); and the Clinical Lipidology and Rare Lipid Disorders Unit, Department of Medicine, Université de Montréal Community Gene Medicine Center, Lipid Clinic Chicoutimi Hospital and ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, QC, Canada (D.G.).
Evinacumab significantly reduced LDL cholesterol in patients with homozygous familial hypercholesterolemia, offering a new treatment for this severe condition. This ANGPTL3 inhibitor demonstrated a 47.1% reduction in LDL cholesterol levels.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Pharmacology
Background:
- Homozygous familial hypercholesterolemia (HoFH) causes premature cardiovascular disease due to extremely high LDL cholesterol.
- Genetic variants impairing LDL-receptor activity are the primary cause of HoFH.
- Loss-of-function variants in ANGPTL3 are linked to lower lipid levels and protection against cardiovascular disease.
Purpose of the Study:
- To evaluate the efficacy and safety of evinacumab in patients with HoFH.
- To assess the impact of evinacumab on LDL cholesterol levels in patients with HoFH receiving maximal lipid-lowering therapy.
Main Methods:
- A phase 3, double-blind, placebo-controlled trial involving 65 HoFH patients.
- Patients received either evinacumab (15 mg/kg IV every 4 weeks) or placebo, alongside stable lipid-lowering therapy.
- The primary outcome was the percent change in LDL cholesterol at 24 weeks.
Main Results:
- Evinacumab demonstrated a 47.1% relative reduction in LDL cholesterol at 24 weeks, compared to a 1.9% increase in the placebo group.
- The between-group difference in LDL cholesterol reduction was -49.0 percentage points (P<0.001).
- Adverse events were comparable between the evinacumab and placebo groups.
Conclusions:
- Evinacumab significantly reduces LDL cholesterol in HoFH patients on maximal therapy.
- This ANGPTL3 inhibitor represents a promising therapeutic option for managing HoFH.
- The study highlights the role of ANGPTL3 in severe hypercholesterolemia.
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