Regeneron claims breakthrough badge for Praluent sidekick evinacumab

Drug could be a new option for tough-to-treat generic cause of high cholesterol

The FDA has awarded Regeneron breakthrough status for evinacumab, a potentially first-in-class drug designed to help patients who struggle to meet cholesterol targets despite current therapies.

The regulatory authority has given the tag to the ANGPTL3 inhibitor for homozygous familial hypercholesterolemia—a particularly insidious and life-threatening genetic cause of high cholesterol that leads to accelerated cardiovascular disease, sometimes as early as childhood if untreated.

HoFH patients continue to have major problems managing their cholesterol levels as they are typically not as responsive to standard lipid-lowering therapies such as statins or even to the new PCSK9 inhibitor such as Regeneron and Sanofi's Praluent (alirocumab) and Amgen's Repatha (evolocumab).

ANGPTL3 acts as an inhibitor of lipoprotein lipase and endothelial lipase, two enzymes thought to play a central role in lipoprotein metabolism, says Regeneron, which would love to slot the drug in alongside Praluent in its cardiovascular portfolio.

Last year, Regeneron reported a positive midstage trial for evinacumab showing that adding the drug to standard therapy resulted in an additional 55% reduction in LDL-cholesterol, following it up with phase 1 data in healthy volunteers that demonstrated its ability to cut elevated triglycerides, which raise the risk of atherosclerosis as well as other complications like inflammation of the pancreas. The company says it is now gearing up to launch a phase 3 trial in HoFH.

The two sets of results—plus positive phase 1/2 data from Ionis' subsidiary Akcea's rival drug IONIS-ANGPTL3-LRx which was reported at the American Heart Association meeting last November—has made investors sit up and take notice of evinacumab.

Previously it was viewed as a fairly speculative program, not least because of the slow takeup of the PCSK9 inhibitors as they try to convince payers of their clinical value over and above low-price generic statins. As recently as last September, analysts at Credit Suisse were giving evinacumab only a 5% chance of approval by 2022, while Sanofi's decision not to partner the drug also undermined confidence in the program.

Undeterred, Regeneron ploughed on, with the drug's program director, Bill Sasiela, Ph.D., describing ANGPTL3 as "a new and exciting target that we look forward to exploring further in additional clinical trials." The breakthrough status award suggests that confidence may be rewarded.