Biotech Values

[DewDiligence]

Pazdur's Revenge

[This is an editorial from today’s WSJ. The specific issue is whether widespread off-label use of drugs in a given cancer indication should *preclude* a new drug candidate from being considered for accelerated approval in this indication, based on the notion that there is not a compelling “unmet medical need.” The FDA’s Richard Pazdur evidently thinks that accelerated approval should be precluded, or at least made more difficult to obtain, but there may be no statutory authority for such a viewpoint.]

http://online.wsj.com/article/0,,SB110350558746504451,00.html?mod=opinion%5Fmain%5Freview%5Fand%5Fou...

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We've been worried that overreaction to the Vioxx withdrawal could easily end up doing far more damage to public health than that drug ever did. And we're sorry to report that so far this is exactly where we're headed.

The trial lawyers, for starters, have launched a campaign of unprecedented size and scope that threatens the R&D budgets not just of Merck but of the entire pharmaceutical industry. That assault is only going to increase after last week's announcement from Pfizer that its COX-2 pain reliever, Celebrex, also showed an increased incidence of heart attacks among some patients at high dosages. At least Pfizer hasn't made Merck's mistake of pulling the drug off the market, since it remains a life-enhancer for millions of arthritis sufferers.

But to appreciate how the lawyers are massing, consider this lip-smacking comment to the New York Times on Saturday from plaintiffs lawyer Richard G. Sullivan: "It's not as big as asbestos and it's not as big as tobacco but it's number three." Just what the U.S. economy needs: The looting of another industry, and one at the cutting edge of global innovation besides.

Meanwhile, Congressional opportunists like Senate Finance Committee Chairman Charles Grassley seem to think the appropriate response is to make it even harder for innovative therapies to get to market. And inside the beleaguered Food and Drug Administration some bureaucrats are using the current political climate as cover to turn back what little progress has been made on drug approval times.

Readers of these columns may remember Richard Pazdur, the FDA's oncology (cancer) drugs chief who featured in our editorials about the Erbitux-ImClone-Martha Stewart debacle. That cancer drug was subsequently approved based on more or less the same evidence Dr. Pazdur thought was insufficient the first time around, and former FDA Commissioner Mark McClellan issued guidelines intended to clarify the accelerated approval process for innovative therapies of its kind. The faster approval concept was a response to protests from AIDS activists in the 1980s and was later extended to cover therapies for other terminal diseases.

But at a meeting of the FDA's Oncologic Drugs Advisory Committee earlier this month, Dr. Pazdur tried to turn back the clock, offering a twisted interpretation of the McClellan guidelines that more or less entirely reversed their original intent.

At issue was a therapy called Marqibo for aggressive non-Hodgkins lymphoma for patients who relapse following initial treatment. While statistically Marqibo doesn't appear to be a magic bullet therapy on the order of Gleevec (a near miracle cure for one kind of leukemia), there was plenty of evidence before the panel to suggest it might have been a valuable addition to the anti-cancer arsenal, given how much variability there is in the way individual patients respond to different drugs.

And since there are no other drugs approved for relapsed non-Hodgkins, it should have been eligible for accelerated approval. But Dr. Pazdur explained that since there are a number of drugs for other conditions being used "off-label" to treat relapsed non-Hodgkins, there was no great urgency concerning Marqibo.

This, according to officials involved in drafting them, was precisely the opposite of what the McClellan guidelines intended to do by defining "available therapies" as approved drugs for a given indication so as to leave open as many accelerated approval pathways as possible. The Pazdur interpretation of the rule would effectively kill the accelerated approval process, since there are off-label therapies for just about everything.

Just as worrying as the fate of this individual therapy was the apparent relish with which some of the panelists dismissed the efforts of Marqibo's makers at the Enzon company and fired back at the patient activists who've been uppity enough to suggest faster access to developmental drugs. As ODAC Chairwoman Silvana Martino questioned the accelerated process generally, Dr. Pazdur was heard to exclaim, "Go girl, go!"

The good news is that Dr. Pazdur may not be holding the fate of tens of thousands of lives in his hands for too much longer. The FDA is merging two units to create a new cancer drugs division, and there's an opportunity to find a new chief from outside the agency who doesn't share his mindset. The bad news is that the Bush Administration has given no indication it understands the importance of having pro-innovation, pro-patient officials in FDA jobs -- especially in a hazardous political climate like the one we have now.

The new nominee for Secretary of Health and Human Services -- former Utah Governor Mike Leavitt -- could get a jumpstart on his new job by contacting former FDA Commissioner McClellan (who's now running Medicare) to discuss a suitable permanent replacement. Vioxx and Celebrex notwithstanding, far more people die every year for lack of developmental drugs than die from taking approved therapies, and the FDA is simply too important to be left leaderless at a time like this.
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