Regeneron's Evinacumab Shows Significant LDL-C Reduction in HoFH Patients, BLA Filing Planned for Q2

On the 31st, Regeneron presented detailed results from its Phase 3 clinical trial of evinacumab for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) at the American College of Cardiology’s Annual Scientific Session jointly held with the World Heart Federation (ACC.20). Evinacumab is a fully human monoclonal antibody targeting angiopoietin-like protein 3 (ANGPTL3). The trial results demonstrated that evinacumab further reduced low-density lipoprotein cholesterol (LDL-C) levels by 49% in HoFH patients already receiving statins and PCSK9 inhibitors. The company plans to submit a Biologics License Application to the U.S. Food and Drug Administration (FDA) in the second quarter of this year.

Homozygous familial hypercholesterolemia (HoFH) is a severe, rare genetic disorder. Patients with HoFH exhibit markedly elevated low-density lipoprotein cholesterol (LDL-C) levels, which frequently lead to premature atherosclerotic cardiovascular disease and can sometimes cause heart attacks even during adolescence. Despite treatment with existing lipid-lowering therapies, their mean LDL-C level remains at 255 mg/dL, significantly exceeding the safety threshold of 100 mg/dL.

Evinacumab is a monoclonal antibody targeting ANGPTL3. ANGPTL3 is an inhibitor of lipoprotein lipase and endothelial lipase, playing a critical role in lipoprotein metabolism. It was granted Breakthrough Therapy Designation by the FDA in 2017 for the indication of HoFH.

▲ Studies have shown that inhibiting ANGPTL3 helps prevent cardiovascular disease (Image source: Reference [2])

In the Phase 3 ELIPSE clinical trial, patients with homozygous familial hypercholesterolemia (HoFH) received evinacumab or placebo in addition to other lipid-lowering therapies. Among these patients, 95% were using statins and 79% were using PCSK9 inhibitors. The trial results demonstrated that after 24 weeks of treatment, the evinacumab group achieved a 49% reduction in LDL-C compared to the control group (p<0.0001). Furthermore, 47% of patients in the evinacumab group achieved LDL-C levels below 100 mg/dL, compared to 23% in the control group.

“As a physician, it is heartbreaking to see patients with homozygous familial hypercholesterolemia (HoFH) struggle to lower their life-threatening LDL-C levels,” said Dr. Derick J. Raal, Professor in the Department of Endocrinology and Metabolism at the University of the Witwatersrand, South Africa. “In this clinical trial, HoFH patients treated with evinacumab were able to reduce their LDL-C levels to previously unattainable ranges, with nearly half achieving levels considered ‘normal’ for healthy adults.”

Dr. George D. Yancopoulos, President and Chief Scientific Officer of Regeneron, stated: “Evinacumab is a unique antibody with a mechanism of action distinctly different from other therapies for HoFH. This exemplifies the delivery of revolutionary therapies to patients through genetics-driven research.”

References:

[1] REGENERON ANNOUNCES AMERICAN COLLEGE OF CARDIOLOGY PRESENTATION OF POSITIVE PHASE 3 EVINACUMAB RESULTS IN PATIENTS WITH SEVERE INHERITED FORM OF HIGH CHOLESTEROL. Retrieved March 30, 2020, from https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-american-college-cardiology-presentation

[2] Stitziel et al., (2017). ANGPTL3 Deficiency and Protection Against Coronary Artery Disease. JACC, DOI:10.1016/j.jacc.2017.02.030

Flash | LDL Cholesterol Halved: Regeneron’s Innovative Lipid-Lowering Therapy Poised for Marketing Application Submission in Q2

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