Thursday, December 03, 2009

FDA's Jenkins Sounds Off on Incomplete NDAs

Earlier this week, FDA issued a Refuse to File on Merck-Serono's cladribine application, meaning the agency felt the NDA was sufficiently lacking that it didn't want to begin a review yet.

The topic of Refuse to File letters came up today at Windhover's FDA/CMS Summit. No drug or company was mentioned by name, however; the discussion was prompted by an audience question and warmly embraced by FDA Office of New Drugs director John Jenkins.

FDA, Jenkins said, has for the most part held up its end of the bargain created 17 years ago by the industry-FDA agreement known as PDUFA. "Most of the time," he said, FDA reviews drugs in the appropriate time window. But too often industry is developing the drug on FDA's review clock. If industry really expects FDA to stick to that model, he said, applications need to be complete so that questions won't arise just before the PDUFA date because information is still coming in from drug sponsors during the review process.

If industry's complete response letters were released, "would you make sure your application is complete before you submitted it?" asked Jenkins. Would senior executives wake up to regulatory realities? Jenkins suggested that companies "do the math some time." Delaying an NDA a few months until it's truly complete can save double that time on the extended review process that results from incomplete applications.

We can't be sure why FDA dinged Merck-Serono's application; that information is, for now, secret. In a recent feature about potential orally available multiple sclerosis therapies we duly noted that Merck Serono's chances with its first-to-NDA oral therapy cladribine weren't a 'slam dunk'. The drug's efficacy looks great in one Phase III trial in relapsing remitting MS patients, and side effects in this therapeutic space are navigable, for sure (just ask Elan and Biogen Idec). But that's just one trial, as we also noted, and the drug hasn't been tested against an active comparator. It was never clear how FDA would react to that.
FDA's rebuttal might have been due to some other deficiency unrelated to the lack of a confirmatory Phase III trial (which will take the company many more than just a few months, given the time frames for large MS trials). For its part the company has stated that it will get together with FDA as soon as possible to discuss the issue and other Phase III studies of oral cladribine which are ongoing in different forms of MS.

image from flickr user wilhei55 used under a creative commons license

1 comment:

Brian Orelli said...

Good to know that the agency doesn't just has a thing for companies with Merck in their name.

American Merck disclosed a refuse to file at the beginning of November for MK-0653C.