26 Aug Homozygous Familial Hypercholesterolemia: FDA Accepts Regeneron’s Monoclonal Antibody Evinacumab for Priority Review

MedicalResearch.com Interview with:

Professor F. J. Raal

Professor F. J. Raal, FRCP, FCP(SA), Cert Endo, MMED, PhD
Director, Carbohydrate & Lipid Metabolism Research Unit
Professor & Head, Division of Endocrinology & Metabolism,
Faculty of Health Sciences, University of the Witwatersrand

 MedicalResearch.com: What is the background for this study?

Response: The objective of this randomized phase 3 study was to evaluate the efficacy and safety of evinacumab in adult patients with homozygous familial hypercholesterolemia (HoFH), a condition that remains very difficult to treat. The primary endpoint was reduction of low-density lipoprotein cholesterol (LDL-C) from baseline with evinacumab compared to placebo at 24 weeks. 

MedicalResearch.com: Would you briefly explain what is meant by homozygous familial hypercholesterolemia? How many individuals may be affected by this disorder?

Response: HoFH, or homozygous familial hypercholesterolemia, is the most serious and more rare form of familial hypercholesterolemia (FH).  It is estimated that as many as 1 in 300,000 people worldwide and approximately 1,300 people in the U.S. are affected by HoFH. A person who has HoFH has inherited two FH genes, one from each parent. They therefore have LDL-C levels that are elevated 4-fold or greater from birth and are at high risk for premature atherosclerotic disease and cardiac events which can occur in childhood. While current treatment guidelines recommend early and intensive LDL-C lowering, people with HoFH tend to be less responsive (or unresponsive) to standard lipid-lowering therapies, including high-intensity statins and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors and often require lipid apheresis.

MedicalResearch.com: How is evinacumab different from other lipid lowering medication?

Response: Unlike statins and PCSK9 inhibitors which act mainly by upregulating LDL receptor function, evinacumab targets angiopoietin-like 3, or ANGPTL3. Inhibition of ANGPTL3 by evinacumab lowers LDL-C independently of LDL receptor function. Evinacumab is the first investigational medicine of its kind to show efficacy in patients with homozygous familial hypercholesterolemia, including those with little to no low-density lipoprotein (LDL) receptor function.   

MedicalResearch.com: What are the main findings of the underlying studies?

Response: The trial demonstrated that adding evinacumab to other lipid-lowering therapies cuts LDL-C or “bad cholesterol” levels in half in patients with homozygous familial hypercholesterolemia. Specifically, the trial met its primary endpoint, showing that patients treated with evinacumab (n=43) reduced their LDL-C from baseline by 49% compared to other lipid-lowering therapies with or without lipid apheresis (placebo, n=22) at week 24 (47% reduction evinacumab, 2% increase placebo, p<0.0001). There were no deaths, major adverse cardiovascular events or discontinuations due to AEs. It’s important to note that the safety and efficacy of evinacumab in longer term studies have not been fully evaluated by any regulatory authority.

MedicalResearch.com: What should readers take away from your report?

Response: If approved, evinacumab may provide a new option for patients with HoFH who are unable to reach target LDL-C despite multiple conventional lipid-lowering therapies with or without LDL apheresis. Evinacumab may also reduce the need for lipid apheresis in HoFH patients. These patients have significant unmet needs as they would otherwise remain at increased risk of premature heart disease because of persistently high LDL-C levels. 

MedicalResearch.com: Is there anything else you would like to add? 

Response: The full results of the Phase 3 trial were recently published in the New England Journal of Medicine. Professor Raal has received research grants, honoraria, or consulting fees for professional input and/or delivered lectures from Sanofi, Regeneron, Amgen, The Medicines Company and Novartis. 

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Last Updated on August 26, 2020 by Marie Benz MD FAAD