Regeneron, Sanofi Pass First Key Test With Cholesterol-Lowering Drug

10/16/13Follow @benthefidler

Scientists who study cardiovascular disease have been buzzing about the promise of a target called PCSK9 for years. The target is also part of a high-stakes race that pits Regeneron Pharmaceuticals (NASDAQ: REGN) and its development partner Sanofi, against Amgen, Pfizer, and several others who are all in pursuit. While there’s still many laps ahead, Regeneron and Sanofi have become the first to produce some data from a late-stage clinical trial.

Tarrytown, NY-based Regeneron today gave investors a glimpse at the first late-stage clinical trial for alirocumab, a targeted antibody drug designed to block the PCSK9 enzyme and fight cardiovascular disease by lowering cholesterol.

So far, so good: alirocumab met its goal of lowering patients’ low-density lipoprotein (LDL) cholesterol levels more than another alternative to statin therapy—Merck’s ezetimibe (Zetia). The new drug was able to lower LDL cholesterol by about 47.2 percent on average after 24 weeks, compared with 15.6 percent in the control group. The most common adverse events reported during the study were stuffy nose, flu, and upper lung infections, although the incidence was similar for both study groups, Regeneron and Sanofi said. The study enrolled 103 patients. More detailed results are expected to be presented at a later scientific meeting.

The news was encouraging, and Regeneron’s sky-high stock rose a bit more today as a result. But today’s release is only a small part of the overall PCSK9 story. Regeneron and Sanofi plan to enroll more than 23,000 patients total in 12 trials, with the majority of those trials testing the drug in tandem with other cholesterol-lowering drugs such as statins. This initial trial Regeneron released top-line results from today tested alirocumab on its own.

Here’s how the study was designed. A group of 103 patients with high cholesterol and “moderate” cardiovascular risk were randomly assigned to get either Regeneron’s drug, or ezetimibe.

The group getting Regeneron’s drug self-administered it through 12 injections just under the skin over 24 weeks. Those patients were given a 75 mg dose of the drug, though a minority—reportedly 14 patients—had the dose ratcheted up to 150 mg because the lower dose wasn’t strong enough to get the patients down to a pre-specified target LDL level of 70 milligrams/deciliter of blood. The Merck group got ezetimibe over the same time frame.

The study was designed to show that Regeneron’s drug lowered patients’ LDL—better known as ‘bad’ cholesterol—better than Merck’s. Ezetimibe is typically prescribed when people either can’t tolerate statins, or want to boost their effects because their cholesterol isn’t being lowered enough.

Regeneron will have to duplicate results like these on a much larger scale, of course, but the big significance here is that these are the first data released from a Phase 3 trial on a PCSK9-blocking drug. The stakes are high, because many believe that this molecular target represents the next big thing in treating cardiovascular disease. While people with high cholesterol are typically treated with statins—many of which, like atorvastatin (Lipitor) are already generic and cheaply priced—the belief is that PCSK9 blockers can be a valuable option either when combined with statins, or for those who don’t respond well to them. That means a potentially huge market will open up if these drugs can prove to be safe and effective, especially since Lipitor long held the title as the world’s best-selling drug. Given that potential, it’s obvious why alirocumab and competing drugs being developed by Amgen, Pfizer, and others, are being so closely watched. RBC Capital Markets analyst Adnan Butt, for example, is estimating about $3 billion in potential peak sales for Regeneron’s drug, should it make it to market.

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com Follow @benthefidler

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