Genzyme, Isis Cholesterol Drug Reaches Goal in Pivotal Study, Paving the Way to FDA

5/20/09Follow @xconomy

[[Update below]] Genzyme and Isis Pharmaceuticals have bet big on a new kind of cholesterol-lowering drug, and today the companies said it worked in a pivotal clinical trial.

Mipomersen, a drug designed to block production of a protein that carries LDL cholesterol in the blood, reached its goal in a study of 51 patients with a rare genetic abnormality called homozygous familial hypercholesterolemia, that gives them extremely high cholesterol. Patients on the new drug had a 25 percent reduction in their LDL cholesterol counts, compared with a 3 percent drop for those on placebo, and the difference was statistically significant. Full data will be presented later at a medical meeting, the companies said.

The news is important to Cambridge, MA-based Genzyme, because it is carrying out a plan to apply for FDA approval of mipomersen first in this small patient population of 500 or so, while also studying it in much larger groups of patients that might turn the product into a blockbuster. For Carlsbad, CA-based Isis Pharmaceuticals, it’s an important validation of its antisense technology, in which specially engineered strands of RNA drugs are designed to block a problematic protein in the body, which often can’t be blocked by conventional small-molecule drugs. The companies struck a partnership to co-develop the drug in January 2008, which brought $325 million in upfront cash to Isis, and could be worth as much as $1.9 billion to Isis if the drug achieves certain goals in development.

“These are promising results for a very high-risk patient population that is in great need of new treatment options,” said Genzyme chief medical officer Richard Moscicki, in a statement. “This is one of the largest studies of hoFH patients ever conducted, and we are very encouraged by these robust data and the emerging profile of the drug. With these results, we remain on-track with our development plan for mipomersen.”

Besides reaching its main goal of lowering LDL cholesterol, mipomersen achieved all three of its secondary goals in the study of reducing the apoB protein it’s supposed to block, lowering total cholesterol, and non-HDL cholesterol, the companies said. The company said it plans to submit the data to the FDA for approval in the second half of 2010, by which time it hopes to have data from larger trials of mipomersen in other types of patients with high cholesterol.

The most common side effects among the 34 patients who got mipomersen were flu-like symptoms, swelling near the injection sites, and an increase in liver enzymes. One patient dropped out of the study because of an increase in liver enzymes, which can be a sign of liver damage. Patients had to take 200 milligrams of mipomersen through weekly injections for about six months.

Patients entered the study quite sick. They had an average LDL cholesterol score of 400 milligrams per deciliter of blood, even though they were already taking the highest possible dose of the common statin medicines, and other drugs to lower fats in the bloodstream. Any total cholesterol score above 240 is considered high, and anything below 200 is considered desirable, according to the Mayo Clinic.

[[Update 11:15 am Eastern time]] A 25 percent average reduction in LDL scores would bring patients in this study down to an average score of 300 milligrams per deciliter, which for most people is still considered high. Some patients in the trial had their LDL counts drop much more than 25 percent, although those detailed results aren’t being released yet, says Isis spokeswoman Amy Blackley. “There were some really high reductions,” Blackley says.

A previous study showed the drug could lower cholesterol by an average of 49 percent—better than results announced today—but that was in just eight patients, and they took a higher 300 milligram dose, said Isis spokeswoman Amy Blackley. The pivotal study announced today was designed to show at least a 20 percent reduction, and cleared that average hurdle, even when handicapped by factoring in six patients who enrolled but didn’t complete their course of treatment, Blackley says.

“These are patients who are on everything and they still can’t get their LDL down. If you can get it down by 100 points, that’s phenomenal. There’s nothing else for them,” she says.

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  • iguanabio

    pts with HFH can be controlled on apheresis which runs $30-40k/year…a lot cheaper than I’m sure this will be. Plus, the LDL drop is insignificant in patients with 1000+ LDLs. The big prob though is liver tox, and one patient in such a small group is concerning. If the strategy is to go for a larger, less severe population then safety will be key.

    will be difficult

    iguanabio.com