It was an incredibly beautiful week here inside the Beltway with crystal blue skies and today temperatures are going into the mid-80s. A lot has been happening on many fronts, and here is a little of what has happened in our corner of the world:
- I’m a Twittering Fool – I have added a Twitter application to Eye on FDA. You will find it over in the upper left hand corner under my handsome face. In that space I’m posting news as I see it that I think you might be interested in. I will also, when at conferences, Hill hearings or FDA Advisory Committee meetings be able to provide on-site instant updates. If you are really interested, get yourself a Twitter account and follow my twittering!
- Approvable Letter Turns into an Approval – Pozen and GlaxoSmithKline scored a victory this week when the FDA issued an approval for the migraine treatment Treximet. The news sent Pozen’s stock up considerably, by about 34%. According to the press release – "Treximet is the first and only migraine product designed to target multiple mechanisms of migraine by combining a triptan, a class of migraine-specific medicines pioneered by GSK, and an anti-inflammatory pain reliever in a single tablet." Previously the companies had two, count ’em, two approvable letters for the drug. Persistence pays off.
- JAMA Publishes Report on Merck and Ghostwriting – I will write more on this on Monday, and Derek Lowe over at In the Pipeline has an excellent posting on this subject today, but in the meantime, if you are interested in this rather disillusioning development, you can go to the JAMA study called Guest Authorship and Ghostwriting in Publications Related to Rofecoxib. It is an eye-opening account of writing and shopping for authors.
That’s it for me this week. Have a wonderful weekend.
Re: The FDA this Week: Andy’s Take
Andy’s take:
“Each year the US Food and Drug Administration expends considerable resources convening over 60 advisory committee meetings. This is part of our commitment to engage a wide range of scientific expertise to inform our regulatory decision making process. This is the right thing to do for we must keep up-to-date with the rapidly-changing world of science related to the products we regulate”.
Read more here: http://www.fda.gov/oc/vonEschenbach/andys_take/default.html
In light of the circumstances why would Andy make such a statement in his blog. The pending 6th Circuit Court case (CareToLive vs. FDA) states the following in the CTL brief:
The Rolling Review allows the FDA clinicians to review the sections of the data as it comes in and work with the applicant to make sure that they have the proper and required data, rather than waiting to begin their review only after the entire BLA has been submitted. Importantly, the FDA had all the final clinical data supporting the safety and efficacy of Provenge as of August 24, 2006. Between August 24th, 2006 and the issuance of the Complete Response (CR) Letter on May 8th 2007, the FDA actions were contrary to the later capricious assertion that the data were not sufficient to be able to evaluate the safety or efficacy of Provenge. The FDA does not empanel Advisory Committees if there are insufficient data for the experts to make an evaluation. After years of review of the rolling submission and then clinical review of the final application submitted on or about November 15, 2006, the FDA approved the application for filing and assigned it priority review status on January 16, 2007.
…….. It was after a full review by clinicians within the FDA, that it was determined by those clinicians that there were sufficient data to evaluate Provenge. When the FDA accepted the Provenge application and granted Priority Review status to the application, it did so because FDA clinicians determined that there were in fact sufficient data, and because Provenge is a treatment for a life threatening condition for which there are no viable treatment options.
If the application was “incomplete” (lacked sufficient data) the FDA should have, in accordance with regulation, refused to accept it for filing, as it often does. If not for the belief that there were sufficient data to evaluate, the FDA never would have taken the next step, which was to convene an Advisory Committee, who after a full hearing, determined that Provenge was safe and demonstrated substantial evidence of efficacy. If the data in the application were insufficient for evaluation, the FDA should not have evaluated it and wasted tax payer money.
Once the application was accepted rather than “refused to file”, the options available to the FDA were to approve, to not approve, or to grant conditional approval. Asking for “more data” after more than 9 months from submission of the entire clinical portion had passed, is essentially stating that the application was incomplete, something more reasonably determined before accepting the BLA, and before wasting tax payer dollars. It was at the time application was made, not later, that the FDA had the following choice: FDA may (1) refuse to file it if it is incomplete, 21 C.F.R. § 601.2; FDA, “Refusal to File Procedure for Biologics License Applications.
Either the Provenge BLA was complete, containing all necessary data, or it wasn’t. The data didn’t change. If a Biologics License Application (BLA) is incomplete, or in other words, does not contain sufficient data to be evaluated, then it should not be evaluated. Provenge WAS evaluated, including an evaluation by 17 outside experts. The experts, at the time of voting, did not say “I can’t vote yes or no because there are insufficient data”.
Congress has mandated that the FDA (after it has determined that an application is complete and accepts it), convene a panel of experts to help it evaluate treatments such as Provenge. This mandate was issued because Congress recognized that which the FDA recently admitted in a self evaluation subcommittee report http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4329b_02_01_FDA.pdf , that the FDA does not have the resources and the agency experts available to properly evaluate new cutting edge treatments (like Provenge). The report indicated that the main problem areas at the FDA are a weak scientific organizational structure, major gaps in scientific expertise, and an inadequate IT infrastructure, which the subcommittee called disturbing. In addition to recruitment challenges, the turnover rate of the science staff is double that of other government agencies.
This is exactly why the expert AC meetings are so important, and why the FDA acted capriciously when it acted contrary to the opinion of the outside experts recommendations in this matter. The FDA does not have the ability to evaluate these novel new treatments on its own. In this case, a very few individuals, some of whom worked for a competitor of Provenge, were able to override the overwhelmingly positive majority of the AC experts, who overwhelmingly recommended to approve Provenge.
After years of clinical review, the FDA followed the Congressional mandate and empanelled the Advisory Committee of 17 outside experts to assist it in evaluating Provenge. If an AC is empanelled in situations where there are not sufficient data for the outside experts to properly review the application, it not only undermines the Congressional mandate to get safe and effective treatments to cancer patients more quickly, it wastes a huge amount of taxpayer resources. The convening of outside AC panels are extremely expensive for both the applicant and the FDA. This case is a perfect example of an unmet medical need, Fast-tracked given Priority Review status and approved by the AC, all as per the Congressional mandate, but then delayed for improper reasons, thereby achieving the opposite of the mandate to speed treatments along to patients, and instead stalling and resetting the clock in backwards motion, thereby delaying an effective, safe therapy for countless years on end.