The emphasis on safety concerns is, not surprisingly, prompting some people to worry that the FDA may go too far and stymie access to meds - particuarly life-saving meds - by becoming too stringent.

One such person is Richard Miller, the ceo of Pharmacyclics, a small company that is developing Xcytrin, a drug to treat non-small cell lung cancer that metastasizes in the brain. Trials were designed with input from the FDA. Unfortunately, Xcytrin failed to meet its endpoint, which was measuring neurological function instead of survival or disease progression.

Patients receiving Xcytrin plus radiation reported a five-month improvement in measuring neurologic progression, such as memorizing words or walking across a room - compared with patients given only radiation. There was a clinical benefit, but there was also a 12 percent chance that the results occurred by accident. The acceptable stat is 5 percent.

Nonetheless, Miller filed an NDA with the agency, believing the weight of the data justified a look-see. No such luck. The FDA took one look and earlier this year issued a ‘refuse to file’ letter, which is the equivalent of having it marked ‘Return to Sender.’ (Remember that song?)

The agency took a similar approach with Dendreon’s Protenge for prostate cancer; the FDA rejected the recommendation of its advisory panel, which endorsed the med even though it missed its endpoint. In that case, however, Miller notes Dendreon did receive a full review.

And so now, Miller is on a quest. He’s pursuing a ‘File Over Protest,’ which is a way of demanding the FDA review its decision not to review the med. And he’s launched a campaign, which includes the media, to spotlight what he calls an unfortunate paradox. Pharmalot was on his list.

Pharmalot: I get the drift, but you missed a threshhold. Why should the FDA take a look?
Miller: There’s a larger issue here. These are crtically ill patients with few choices. We’re not talking about a drug for a minor illness for which several choices may be available. I don’t think the same standards should be applied for a fatal condition, especially when there’s no other approved treatment available.

Pharmalot: So you’re gripe is that the FDA is missing that point.
Miller: Yes, we think the FDA needs to put things in context. We were required to develop a very robust endpoint that measured profound loss neurologic function, and we did that. It was validated. But the p value just missed. What we’re asking for is the FDA to look at all the data, which I think shows substantial efficacy, and put the data in the context of serious illnesses.

Pharmalot: Why shouldn’t someone think this isn’t really about getting special treatment?
Miller: The FDA has done this before and has a mandate from Congress to do so. In the late 80’s, the AIDS crisis prompted the FDA to do things differently. And there’s no evidence bad drugs came of that or didn’t offer any benefits to the public.

Pharmalot: But what about that p value?
Miller: Statistics are important. I’m not calling for a lowering of standards. But science is changing. There should be more here than an arbitrary cut off. We need to streamline approvals for life-threatening disease. That’s what the Critical Path initiative addresses with its discussion of trying to spur innovation. We shouldn’t be applying some one-size-fits-all approach.

Press release about the filing over protest.

[tags]Pharmacyclics[/tags]