Regeneron's Evinacumab Reduces LDL Cholesterol by 49% in Patients with Homozygous Familial Hypercholesterolemia in Pivotal Phase 3 Trial

Today, Regeneron Pharmaceuticals announced that evinacumab, a therapy targeting the novel angiopoietin-like 3 (ANGPTL3) target, achieved positive results in a pivotal Phase 3 clinical trial. The trial was designed to evaluate the impact of evinacumab on low-density lipoprotein (LDL) cholesterol levels and other lipid-related endpoints. Trial data demonstrated that evinacumab reduced LDL cholesterol levels by 49% in patients with homozygous familial hypercholesterolemia (HoFH) compared with existing lipid-lowering therapies, and was well tolerated. Regeneron plans to present detailed results from this trial at upcoming medical conferences and intends to submit a New Drug Application to the U.S. FDA in 2020.

Homozygous Familial Hypercholesterolemia (HoFH) is a severe, rare genetic disorder affecting approximately 1,300 individuals in the United States. Patients with HoFH experience markedly elevated levels of low-density lipoprotein cholesterol (LDL-C), which frequently leads to premature atherosclerotic cardiovascular disease, sometimes resulting in heart attacks as early as adolescence. Even with current 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 angiopoietin-like protein 3 (ANGPTL3). ANGPTL3 is an inhibitor of lipoprotein lipase and endothelial lipase, playing a crucial role in lipoprotein metabolism. ELIPSE HoFH is an ongoing randomized, double-blind, placebo-controlled Phase 3 clinical trial. In this trial, 65 patients aged 12 years or older with homozygous familial hypercholesterolemia (HoFH) received either evinacumab or placebo while continuing their existing lipid-lowering therapies. These patients had previously been treated with other available therapies, including statins, PCSK9 inhibitors, ezetimibe, LDL apheresis, and lomitapide.

▲Studies show that inhibiting ANGPTL3 helps prevent cardiovascular disease (Image source: Reference [3])

Results at Week 24 after treatment showed that patients receiving evinacumab:

• Compared with the placebo group, LDL cholesterol levels decreased by 49% (a 47% decrease in the evinacumab group versus a 2% increase in the placebo group; p<0.0001).

• Compared with the placebo group, the absolute change in LDL cholesterol levels was 132 mg/dL (a reduction of 135 mg/dL in the evinacumab group vs. a reduction of 3 mg/dL in the placebo group; p<0.0001).

• 47% of subjects had LDL cholesterol levels below 100 mg/dL, compared with only 23% in the placebo group (p=0.0203).

Furthermore, similar reductions in LDL cholesterol levels were also observed in patients with refractory disease who did not respond to other therapies. Compared with the placebo group, evinacumab also reduced apolipoprotein B (ApoB), non-HDL cholesterol, and total cholesterol levels.

A reduction in LDL cholesterol levels was observed as early as Week 2 after treatment initiation and was maintained throughout the 24-week double-blind treatment period.

In addition to the ongoing Phase 3 ELIPSE HoFH clinical trial, evinacumab is also being evaluated in two other Phase 2 clinical trials for the treatment of patients with refractory hypercholesterolemia and severe hypertriglyceridemia.

“Although treatment options have improved in recent years, patients with homozygous familial hypercholesterolemia (HoFH) still have limited choices for lowering LDL cholesterol, and they continue to have a high unmet medical need,” said Dr. George D. Yancopoulos, President and Chief Scientific Officer of Regeneron. “Evinacumab reduced patients’ LDL cholesterol levels by half and demonstrated good tolerability in clinical trials. These results also highlight the potential value of evinacumab for other patients with severe, refractory hypercholesterolemia.”

References:

[1] Regeneron Announces Positive Topline Results from Phase 3 Trial of Evinacumab in Patients with Severe, Inherited Form of High Cholesterol，Retrieved August 14, 2019, from https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-positive-topline-results-phase-3-trial

[2] New Cholesterol-Lowering Drug Receives FDA Breakthrough Therapy Designation Today Retrieved August 14, 2019, from https://mp.weixin.qq.com/s/rbhvQS0iOT3nLNxoJtAQJw

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

Original Title: Express | Regeneron’s New Drug Lowers LDL Levels by 49% in Patients with the Most Refractory Hypercholesterolemia

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