The FDA's prasugrel hearing was "breathtakingly incompetent"

CardioBrief's Larry Husten writes:

As a journalist and editor who’s covered the cardiovascular arena for more than 25 years I’ve tried as much as possible to avoid taking positions on the major controvesies that have appeared over the years. I’m proud that during the “TPA wars” I remained on good terms with not only Eric Topol, Rob Califf and Eugene Braunwald, but Peter Sleight, Charlie Hennekens, and Gianni Tognoni. More recently, as we’ve been engulfed by the Vioxx, Vytorin, and COURAGE controversies, among others, I’ve been pleased to maintain good working relationships with all the mainstream protagonists.

I have no intention of breaking this tradition over prasugrel.

The players in this drama are all far smarter about this kind of stuff than I could ever hope to be, and the subtle statistical and clinical issues are extremely difficult to evaluate and assess. But there is one aspect of the prasugrel story that I do feel competent to comment upon.

The FDA handling of this hearing was breathtakingly incompetent.

Let me explain:

As first reported here previously, less than 48 hours before the advisory committee hearing new member Sanjay Kaul was “uninvited” from the meeting. Now I’m no expert on the criteria for serving on FDA advisory committees, and it’s possible that Kaul’s previous statements represented a legitimate reason for excluding him, but there is absolutely no reason for this to have been done immediately prior to the meeting. It’s not like Kaul was hiding anything. Any reasonable exercise of due diligence– just google “Kaul and prasugrel and you’ll see what I mean– would have revealed his outspoken position. Since Kaul was removed so close to the meeting, and after publication of the roster, FDA officials need to publicly apologize to Kaul and to provide a full explanation for the reasons for his dismissal, and in fact provide an account for the entire sequence of events leading to this last minute debacle.

It’s also not clear what constitutes “intellectual conflict of interest.” But even if there were general agreement that Kaul’s previous positions disqualified him to vote, wouldn’t the committee have benefited from his expertise as a nonvoting member? Other outspoken experts have criticized the FDA hearing for having the atmosphere of a “family picnic.” At the very least, inclusion of someone like Kaul in the proceedings would have allowed the FDA to escape the charge of cronyism and disregard for dissent.

I’m also surprised that there has been little public discussion about the FDA briefing document, which contained apparently redacted content that was easily recovered in the PDF document originally posted on the FDA website. One important point here: some of the redacted content in the document, which appeared to contain information that might have identified patients in clinical trials, or genuine trade secrets, was fully scrubbed from the PDF document and was not recoverable. The recoverable content was more “political” in nature, and appeared to represent a last minute, incompetently executed attempt by top managers at the FDA to stifle opposing views. This pathetic effort to create a sense of unity appears to be typical of the type of managerial problems that have beset the FDA in recent years.

I can’t say for sure whether the prasugrel hearing is a demonstration of intellectual dishonesty or corruption. But I think I can say for sure that it is certainly a clear demonstration of incompetence.

Source

Lilly / Daiichi Sankyo - Effient: Clot Wars continue

Back stories here. And here.

Food and Drug Administration medical reviewers said the agency should approve Effient (prasugrel), a proposed anti-clotting drug being developed by Eli Lilly and Co. and Daiichi Sankyo Co., but should carry tough warnings about bleeding and cancer risks.

Reviews of Prasugrel by different FDA divisions were posted on the agency's Web site Friday.

The drug faces a review Tuesday by medical experts who serve on the agency's cardiovascular and renal drugs advisory committee. The panel is being asked to recommend if prasugrel should be approved for use in certain patients at risk for a heart attack and, if so, what warnings should be placed on the drug.

Last month, a European Medicines Agency committee issued a positive opinion recommending approval of prasugrel. That opinion will be forwarded to the European Commission which grants approval for drugs in the European Union. The commission usually follows that agency's advice.

More at WSJ

Lilly - prasugrel: the FDA's dilemma

A serious internal disagreement has developed within the FDA over whether to approve the new blood thinner as it stands, sources tell the IN VIVO Blog:

The decision to grant priority review in the first place suggests that the top review managers—namely, Office of Drug Evaluation I director Bob Temple and director of the division of cardio-renal drug products Norman Stockbridge—are excited about the potential for the drug.

However, it appears that another party has made a compelling argument against approval of the application in its current state.

Three issues appear to have impeded an FDA decision: (1) the increase in minor and major bleeding and concerns of related deaths in the prasugrel arm; (2) more cancers discovered in the prasugrel group compared to clopidogrel in the TRITON study; and (3) a recent formulation issue either related to the active ingredient or excipient substance.

Bottom line: A delay until spring next year.

More

Lilly - Effient: will prasugrel make it?

On balance, yes.

But the big question will be: if its a bit more effective but causes more side effects where will it be positioned?

It could depend on the price.

Vytorin - a drug that dodged scrutiny

The Ledger writes:

The study that sent Merck and Schering-Plough stock plung ing and put doctors in a tizzy this week did not find any harm from taking the drug Vytorin -- except to pocketbooks.

The problem was that while there was no harm, there was not much benefit either. Vytorin, which combines Merck's drug Zocor and Schering-Plough's Zetia, does not seem to clear arteries any better than taking Zocor alone -- and generic Zocor sells for a mere one-fifth of Vytorin's price.

The other problem for the pharmaceutical giants is that some members of Congress are investigating whether the companies delayed the release of the study's not-so-good news to protect profits for as long as possible.

If so, they did it at the expense of stockholders as well as consumers and insurance programs, including Medicaid and Medicare, which paid for Vytorin when cheaper Zocor would have done. Was the combined drug about science or a market device to up the price of one old drug by dressing it up as something new?

There are still unanswered scientific questions. Merck and Schering-Plough chose to study Vytorin in patients with an elevated genetic predisposition for very high cholesterol. Vytorin reduced the so-called bad cholesterol levels although not as low as target levels set by experts.

Reducing the buildup of plaque on artery walls is the business end of cholesterol control, and Vytorin did not perform any better than plain old, cheap Zocor. Why not? Might the results be different in a more typical population? In a larger study?

Those are important questions. So is this one, for Congress and the Food and Drug Administration: Why is it that Vytorin has been on the market for years, has saturated consumer and medical minds with $140 million a year in advertising and raked in more than $5 billion in sales -- yet we're just getting around to finding out if it works?

Insider's view: Hear hear!

The FDA should, and will, be more cautious when approving NCE's like ezetemibe based only on weak surrogate endpoints.

Pargluva was stopped with a request for harder data.

I wonder which drugs in development will now have the bar raised for them!?