Tuesday, February 26, 2008

FDA, You’re a Heartbreaker

It seems like FDA has been breaking dates--and hearts--left and right these days.

So far this month, the agency has canceled three advisory committee meetings, including two last-minute cancellations by the anti-infective drugs division: Theravance’s telavancin (February 27) and Basilea/Johnson & Johnson’s ceftobiprole (February 28). Both antibiotics are pending at FDA as treatments for complicated skin and skin structure infections.

And that’s on top of the earlier cancellation of a February 20 pulmonary-allergy drugs advisory committee for Jerini’s icatibant (proposed tradename Firazyr), for the treatment of attacks of hereditary angioedema.

FDA certainly has canceled or postponed advisory committees meetings before, but it’s unusual to have three cancellations so close together. And it’s really unusual for the agency to cancel a meeting with such little notice to the sponsor. (Theravance had just three day’s notice, and had already previewed part of the committee briefing documents with investors.)

Is it coincidence, or something else altogether?

There are a few ways to look it:

(1) The optimistic view: FDA is so confident of the quality of an NDA that it decides it doesn’t need its outside experts to weigh in on an application. In general, products that don’t have an advisory committee review have a much easier time at FDA, with a better chance for a first-cycle review.

(2) The pessimistic view: FDA finds enough deficiencies with an NDA that it determines it’s not even worth holding a meeting. Pessimists would argue that the cancellations are indicative of an overall tougher regulatory environment.

(3) The lack-of-resources view: FDA is so budget- and personnel-stressed that it simply cannot afford to hold a meeting.

And here’s one other thing to consider: under the FDA Amendments Act, the agency must hold an advisory committee meeting for every new molecular entity that crosses a reviewer’s desk, or provide a written explanation as to why a meeting is not needed. So perhaps FDA scheduled the advisory committee meetings as required under FDAAA, but then decided they weren’t necessary.

But unfortunately for the drug sponsors, it looks like the pessimistic view is the correct interpretation.

According to FDA’s communications office, all three meetings were canceled “to allow time for the FDA to review and resolve several outstanding issues.” A meeting “was not appropriate at this point” for any of the applications, the agency said. “FDA will continue evaluating the data and will schedule an AC meeting as needed.”

So that’s certainly not good news for Theravance, J&J and Basilea. But it has broader implications as well.

For antibiotic drug sponsors, the cancellations open up the possibility that the anti-infectives division may have bigger-picture issues to work out before the NDAs can be considered. And for all of industry, they serve as yet another reminder that FDA can pull the rug out from under a sponsor at the last minute. For a drug sponsor, that's heartbreaking.


Anonymous said...

This article is innacurate and misleading. In no way did the FDA’s communications office state that the meetings to discuss icatibant or ceftobiprole were canceled “to allow time for the FDA to review and resolve several outstanding issues.” This statement was made specifically for the cancellation of the telavancin panel. No reasons were given for the cancellation of the icatibant or ceftobiprole panels.

Kate Rawson said...

Thanks for your comment. According to our email conversations with FDA's communications office, the agency canceled all three advisory committees for the same reason -- to review outstanding issues. That is usually the reason that FDA cancels advisory committee meetings.

Anonymous said...

It would be interesting to know the details of your communication. I agree that if you speak to the FDA communications people - who are not always that informed. They will agree for all three that a meeting “was not appropriate at this point” and that the “FDA will continue evaluating the data and will schedule an AC meeting as needed.” This goes without saying as both reviews are ongoing. However, only for the telavancin cancellation did the FDA specifically state in its public communications (not in a private and unofficial e-mail) that it was cancelled “to allow time for the FDA to review and resolve several outstanding issues.” I believe these are important distinctions that would become clear if you had taken time to contact any of the sponsors involved.

Kate Rawson said...

We did contact the sponsors, and they chose not to respond. There are usually three reasons for FDA to cancel an advisory committee meeting 1) scheduling problems; 2) additional time to review outstanding issues; and 3)FDA decides that it doesn't need an outside opinion after all (which can be good or bad news for the sponsor).

If a trusted FDA source tells me something on the record, I have to believe it's true. That said, if you have information that contradicts those statements, please feel free to contact me. I would be more than happy to report it.