It appears that Genzyme
Isis is testing mipomersen in patients with homozygous familial hypercholesterolemia (hoFH), a rare genetic disorder that results in extremely high cholesterol levels. The drugmaker thought the agency would approve the drug based on a single laboratory study for cancer with the second one being turned in after the approval. Instead, the FDA wants both test results before the drug can be approved, and that will push the expected marketing date back about a year.
It's much better for the companies to know now that they need to complete the other trial than to have the FDA bring up in an approvable letter the possibility that the drug could cause cancer, as was the case for Pozen
Also of note last week, the FDA said it will require the companies to prove only that mipomersen lowers cholesterol in hoFH patients. But to be approved to treat patients with less-severe cholesterol levels, the companies will need to run a longer trial to show that the drug not only lowers cholesterol but also results in fewer cardiac events, such as heart attacks. The agency is obviously being cautious after Merck's
The non-hoFH patients are still at high risk, because their cholesterol isn't going down significantly enough with their other medication. That makes the patients pretty sick, so the trial shouldn't take nearly as long as studies currently under way by Merck and Schering to measure cardiac events in more general populations. In fact, the companies are hoping to start the trial by the beginning of next year and complete it around 2011.
The deal that was announced last January between Isis and Genzyme hasn't been completed yet. I doubt that the deal will change much from its original value of more than $1.8 billion, but I wouldn't be surprised if any milestones that might have been tied to the phase 3 trial results were moved to the later-concluding carcinogenicity tests.
Given that this is a timing issue only and that there's no indication that the drug won't be approved, the 29% haircut investors gave Isis on Friday might have been a little extreme. Investors willing to wait a little longer for royalties can get in for a little cheaper now.