FDA Calls Regeneron's Evinacumab a Breakthrough

April 6, 2017
By Alex Keown, BioSpace.com Breaking News Staff

TARRYTOWN, N.Y. – The U.S. Food and Drug Administration gave Regeneron a boost this morning after the regulatory agency gave Breakthrough Therapy Designation status to its hypercholesterolemia drug, evinacumab, the company announced this morning.

Evinacumab is an investigational monoclonal antibody to angiopoietin-like protein 3 (ANGPTL3) being developed to treat patients with Homozygous Familial Hypercholesterolemia (HoFH). ANGPTL3 acts as an inhibitor of lipoprotein lipase and endothelial lipase. The company said it appears to play a central role in lipoprotein metabolism. In its statement this morning, Regeneron said the FDA granted the Breakthrough Therapy Designation based on positive interim Phase II results for evinacumab in HoFH patients.

Regeneron released the interim data in May 2016. The interim data from the first four patients treated showed that “evinacumab added to current lipid-lowering therapy reduced low-density lipoprotein cholesterol (LDL-C) levels by an additional 55 percent,”… at week four compared to baseline. Among these four patients, the percent reductions in LDL-C ranged from 25 to 90 percent. All four patients received maximum doses of statin plus ezetimibe with one patient additionally receiving lomitapide 20 mg, the company said. Evinacumab was generally well tolerated and there were no adverse events leading to discontinuation. The most common drug-related adverse events were injection-site reactions, which were mild in severity, according to the interim data.

Hypercholesterolemia is an inherited disorder that can lead to premature cardiovascular disease due to very high levels of LDL cholesterol. HoFH is the most severe form of hypercholesterolemia. HoFH is a rare disease, occurring in approximately one or two people per million, Regeneron said. If untreated, patients with HoFH can see their LDL cholesterol levels skyrocket to levels ranging from 500 to 1000 mg/dL, compared to normal LDL cholesterol levels of less than 130 mg/dL. With the high cholesterol levels, patients are in danger of premature cardiovascular disease. Without treatment, patients typically present with signs and symptoms of atherosclerotic cardiovascular disease before the age of 20, Regeneron said.

Evinacumab is not the only cholesterol-lowering drug in Regeneron’s arsenal. In 2015, the FDA approved Praluent, a PCSK9 inhibitor, to treat patients with heterozygous familial hypercholesterolemia, an inherited condition that causes high levels of LDL cholesterol. Praluent was co-developed with Sanofi .

Regeneron is planning to conduct a Phase III trial of evinacumab, but did not provide a timeline in its announcement.

New York-based Regeneron is not the only company developing treatments for HoFH. Newly-formed Novelion Therapeutics , formed out of the merger of Aegerion Pharmaceuticals and Vancouver-based QLT Inc., has Juxtapid in its pipeline to treat HoFH.