As promised, Pozen (Nasdaq: POZN ) and partner GlaxoSmithKline (NYSE: GSK ) announced yesterday that the pair had submitted a response to their approvable letter, but it was the second half of the press release that should have peaked investors' interest.
Back in August, the companies received a second approvable letter for Trexima, because the FDA was worried about a pre-clinical assay that showed the drug combination caused DNA damage. The companies think they can convince the FDA that the DNA damage is an artifact that wouldn't occur in humans -- thus the response to the approvable letter. Still, just to be on the safe side, the companies are launching a clinical trial to show that the drug doesn't cause DNA damage in humans. It doesn't sound like the companies are too convinced that the response will be enough, does it?
The artifact argument revolves around the differences between the cells used in the pre-clinical DNA damage assay, which are derived from ovaries of Chinese hamsters (CHO), as well as human cells. Essentially, the CHO cells are more susceptible to DNA damage and therefore not a good indication of the likelihood that Trexima will cause cancer.
While I think this argument is sound, and I'd agree it's the most likely explanation for the result -- given that two other assays showed no DNA damage -- I'm just not sure the FDA is going to agree. The agency's main concern, especially after Merck's (NYSE: MRK ) Vioxx issue, is the safety of the drug. And what better way is there to test the hypothesis that it won't hurt humans than to do a clinical trial?
The good news is the safety trial should be relatively quick, with patients being dosed and having a blood draw to look for DNA damage in their white blood cells in about 10 days. The bad news is that the analysis of the DNA damage is very labor-intensive and the data won't be ready until about the end of February. The FDA could take up to six months to make a decision about the response, so the companies might be able to amend their response with the new trial data without having to extend the review any further.
As I said in my previous article, I think Pozen is making the right move by submitting the response arguing that it's an artifact -- especially given the time constraints. But I think it's more likely that the FDA will want to see the safety trial data before approving the drug, and that makes the announcement of a safety trial an even better move.