FDA to Biotech: Don't Blame Us For Your Cruddy Data
For the past few years, a coterie of biotech executives, desperate patients and ideologues have waged a low-level but steady campaign to convince the country that the Food and Drug Administration is condemning sick Americans to death by denying them potentially life-saving cancer drugs and other treatments. For all three, it's a no-brainer: Biotechs want their drugs approved faster, under laxer standards; terminal patients believe that newer drugs might offer them hope of survival, however slim; and economic conservatives believe the FDA is a blight on the free market.
For instance, see just about any WSJ op-ed piece by Richard Miller, CEO of the small biotech Pharmacyclics, who frequently argues that FDA requirements that drugs prove themselves in rigorous clinical trials has slowed medical progress. (Miller doesn't tend to mention quite as frequently that the FDA rejected his company's brain-cancer drug Xcytrin last year because it didn't seem to work.)
Of course, such arguments also serve as cover for unscrupulous drugmakers -- usually biotechs -- who try to game the FDA-approval process with dressed-up data and heartbreaking pleas from terminally ill patients. So far, however, that's generally been a losing strategy.
Last year, for instance, the biotech Dendreon sought approval for a prostate-cancer vaccine based on two tiny trials whose statistics the company had already shamelessly tortured. When the FDA instead required more data, necessitating a delay of several years, cancer patients erupted in fury, conspiracy theories coalesced into a frivolous lawsuit and free-market conservatives worked themselves into a lather denouncing the FDA. All to no avail, as it turned out.
One of the main obstacles to such efforts has been Richard Pazdur, head of the FDA office that oversees cancer drugs and a hardcore believer in the need for strong medical evidence of a drug's safety and effectiveness. (As such, he's also Public Enemy No. 1 for much of the biotech industry.) Pazdur recently sat down for a brief interview with BusinessWeek, during which he offered some rare insight into FDA's perspective on why many cancer drugs fail and the games biotech companies frequently play to hide the shortcomings of their experimental drugs:
The FDA is often criticized for being too conservative when it comes to cancer drug reviews, particularly by biotech companies. But these companies also lack regulatory experience. How would you apportion the blame, if any?Final emphasis mine. Pazdur's pithy formulation here skewers the false assumption at the heart of the "open the floodgates" argument, which is that these drugs might work just fine if only the FDA would get out of the way. Of course, FDA has a legal responsibility to ensure that drugs are safe and effective, and half-measures in that regard -- testing whether a drug shrinks tumors, for instance, instad of whether it helps patients live longer -- have repeatedly proven inadequate as a measure of a new treatment's actual potency. With no good data that a drug actually benefits people, the FDA really doesn't have any choice but to slam on the brakes and ask for more better trials.
One of the things we have seen is a reluctance, sometimes, of smaller companies to make really critical decisions regarding their drugs, whether to curtail the development of a drug. Large companies, because they have a portfolio of drugs, generally if a drug fails to meet specified goals they'll look to abandon that drug--i.e., cut their losses. Whereas as a smaller company, if you only have one drug, then sometimes that is not an option.The big pharmaceutical companies don't want to waste their time with the FDA. They want to have a long-term relationship with the FDA. They certainly don't want to have to plea to the FDA that the drug should be used and marketed, even though it doesn't work, on an emotional basis.
There is considerable discussion in the drug industry about looking at how a drug performs in subgroups of trial participants, even if it has failed to meet its goal in the larger trial. What is your view of this approach?
One of the problems we've had is people coming to us after a drug fails because they've invested millions and millions of dollars into a drug; and then it's, "How can we salvage this?" In other words, failing your primary endpoint and then trying to salvage a trial by looking at subgroups of patients. That's akin to shooting an arrow and having it land on a wall and then drawing a target around it. It's an attempt to resurrect a trial that has failed.
All this stuff matters for industry because biotechs can blow through hundreds of millions of dollars developing experimental treatments, money that's essentially flushed down the toilet if the FDA issues a late-stage rejection. Doing so on the mistaken assumption that marginal drugs can be "talked past" the FDA not only wastes time and tarnishes the reputations of the executives involved, it also works directly against the interests of patients -- the very people biotechs are claiming to help -- by failing to produce the solid evidence that doctors and insurers need to treat people appropriately.