Genzyme, Isis Cholesterol Drug Passes Pair of Clinical Trials; Shares Fall Anyway

Xconomy Boston — 

Genzyme has been all over the news in the past week because of takeover speculation, but today when fundamental news came out about one of its most important assets for the future, investors yawned.

Cambridge, MA-based Genzyme (NASDAQ: GENZ) and its partner, Carlsbad, CA-based Isis Pharmaceuticals (NASDAQ: ISIS) said today that their drug for people with severely high cholesterol passed a pair of clinical trials. The drug, mipomersen, has now passed a total of four pivotal clinical trials, and the companies are preparing to seek clearance in early 2011 from regulators to start selling the drug in the U.S. and Europe.

Isis, which relies more heavily on this product for its future financial success, saw its shares drop 5 percent to $9.49 at 11 am Eastern time, while Genzyme stock dropped 1.6 percent to $69.07.

Expectations have been high for this drug to become a hit for a couple years now, as the next big thing for cholesterol after the patents expire on multi-billion dollar statin drugs such as Pfizer’s atorvastatin (Lipitor). Genzyme was said to have outhustled more than a dozen rivals that wanted to co-develop mipomersen, and it paid a whopping $325 million in upfront cash, plus $1.9 billion in potential milestone payments, (and potentially much more in future profit-sharing), to get a piece of ownership in this drug back in January 2008.

There’s so much interest for a few reasons. While statins have been used by millions of people to lower cholesterol for more than a decade, there’s a need for stronger cholesterol-lowering drugs for patients who can’t get their levels under control with conventional statins. The new drug is also based on new science, in that it’s designed to use specially engineered strands of RNA drugs to block a problematic protein in the body, which often can’t be hit by conventional small-molecule drugs. In this case, mipomersen is engineered to block the production of a protein called apoB that carries the so-called “bad” LDL cholesterol in the bloodstream. Isis CEO Stanley Crooke told me last October that mipomersen represents the third “remarkable” advance he’s seen in his 30-year career in drug development.

So what did today’s results actually tell us? The first study enrolled 58 patients who were randomly assigned to get a once-weekly injection of mipomersen, or a placebo, for about six months. The patients entered the study with severely high cholesterol—a median LDL count of 276 milligrams per deciliter of blood, even though they were already taking the highest tolerable dose of statins. By the end of the 26-week study, patients on mipomersen saw their cholesterol score drop 36 percent to a more manageable 175 milligrams per deciliter.

Still, not everybody in the trial was motivated to stick with the mipomersen regimen. Of the 39 patients who got the drug, eight dropped out of the study because of adverse events, Isis and Genzyme said. For comparison, just one of the 19 placebo patients dropped out because of an adverse event, the companies said. Researchers also saw increased levels of liver enzymes in mipomersen patients, which can be a sign of liver damage, although there were no reported cases of actual liver damage.

The second study enrolled 158 patients who weren’t as sick—they were classified merely as having a high risk of developing heart disease. More than half of the patients also had diabetes. Patients entered the study with a median LDL cholesterol score of 123 milligrams per deciliter, and when they got mipomersen, they saw that figure drop 37 percent on average to 75 milligrams per deciliter. Half of the patients got to below 70 milligrams, which is a treatment goal for high-risk heart disease patients, the companies said.

“We are pleased with the robust efficacy of mipomersen across all four phase 3 trials. These data, along with the emerging safety profile, support our focused approach on patients at highest cardiovascular risk who are in the greatest need of new treatments,” said Genzyme senior vice president John Butler, in a statement.

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