Why Did the FDA Decide to Flunk Dendreon's Provenge?

Open letter to FDA:

To whom it may concern,

I'm not sure just who it is that is in charge of the FDA. I was under the assumption Dr. Andrew Von Eschenbach was the FDA Commissioner, but after listening to his speeches--and then witnessing Dendreon's (DNDN) Provenge outcome--it is glaringly apparent that Dr. Von Eschenbach is not the leader of the FDA. Instead of addressing my concerns to any particular person(Von Eschenbach, Goodman, Whitten), group (ODAC, CDER, CBER), or FDA Advisory Committee Panelist (Hussain, Scher)---I will simply address my concerns to "whom it may concern." This is under the assumption that, indeed, someone within or involved with the FDA is concerned.

As stated above, my assumptions can be horribly wrong. I assume practically every single FDA employee/associate is at least somewhat aware of Provenge and the FDA's recent "non-acceptance" of timely Provenge marketing. I won't go into all the details, as I assume the FDA is fully aware of said details. I would, however, like to ask a few questions that might clarify some of my concerns about the Provenge marketing delay.

1. Does the FDA believe it has protected late-stage prostate cancer patients by this decision? These men have NO other safe choice....is death a better alternative?

2. An FDA Advisory Committee Panelist voted "YES" for the efficacy of Provenge...and then added something to the effect of (paraphrased) "If I had PC, I'd want Provenge BEFORE chemotherapy." Should this man with vision have "leaked" a letter as Dr. Scher and Dr. Hussain did? Are post-FDA Advisory Committee "letters" needed for a successful approval?

3. Are FDA Advisory Committees a needed step in the approval process? What is the purpose of these committees? The AC vote for Provenge Safety was 17-0(100%). The AC vote for Provenge Efficacy was 13-4(76.4%). 75% of "NO" voters were granted COI waivers. Even if two additional NO votes are allocated for the "leaked letters", the Efficacy vote is still 13-6(68.4%)

4. Should conflict of interest waivers be considered for Voting FDA Advisory Committee Panelist participation? Are such COI waivers actually the reason for the post-FDA Advisory Committee "leaked letters" in the Provenge case?

5. 34% of Provenge patients were alive after three years----only 11% of "placebo" patients were alive after three years. Is it possible to "fake" overall survival? Is overall survival outcome in this(or any) trial really "post-hoc"? Can overall survival be data-mined or is overall survival really the most accurate, easiest to measure, best, and most difficult to achieve endpoint? Eduardo Garcia spoke at the FDA Advisory Committee. Mr. Garcia believes Provenge saved his life. I\\'ve seen two other men on television say the same thing. Ken, a PC survivor, is featured on the cover of the most recent Dendreon Annual Report. Ken is washing his hot-rod....thanks to Provenge (he believes).

6. How many older men who have "miraculously" recovered from the ravages of Prostate Cancer need to be seen washing their hot-rods before other men have the FDA given right to take the chance on Provenge? Does the FDA really want these men to simply accept death?

7. I know my answers to these questions, as I'm in agreement with the visionary mentioned above in #2. If you were diagnosed with PC, would you want to try Provenge? If a loved one had PC, would you want him to have access to Provenge? If a loved one had PC and was unaware of Provenge, would you inform him of Provenge?

8. I'll end my questioning with a rehash. Does the FDA believe it has protected late-stage prostate cancer patients by this decision? These men have NO other safe choice....is death a better alternative? I hope my concerns will concern someone within the FDA. The proper decision on Provenge seems fairly obvious to me. There is time to right this wrong before too many PC victims become FDA victims as well. How many will be "too many"? That's for the almighty FDA to decide.

A Concerned American,

Kelly Holloway

Disclosure: Author has a long position in DNDN

Comments

[hpski:]

I recently posted a comment re: Echo to All's post, focusing on the regulatory history of thalidomide. Your merging of humanity with scientific principle is appreciated, and obviously in short supply amongst a significant majority of White House political appointees – why should FDA be any different? The link below is another slice of oncology product history, as it pertains to FDA's approval of Gemcitabine (Gemzar) for pancreatic, ovarian & lung cancer. The pivotal pancreatic study was very light on patients, but strong on p values. TTDP was increased by 1.2 months, median survival by 1.5 months, but the survival range in the control group, treated with standard 5-FU extended out to 12 months, vs. 9.4 months in Gemzar patients. No objective tumor responses were observed. In ovarian cancer, when combined with Carboplatin vs. Carbo alone, there was no survival advantage, yet progression free median survival was increased by 2.8 months. The overall and complete response rates had a p value of .11. In lung cancer, although median TTDP was increased by a month, there was no survival advantage. Are you sitting down? Survival was the endpoint. The secondary endpoint was quality of life – that wasn’t met either. Bottom line, Gemzar was initially and subsequently approved on threads of data because it offered some hope, and subsequently the $$ flowing to the sponsoring company, E. Lilly, helped fund additional studies, which expanded its use. Additionally, it helped & enabled a very, very smart oncologist, who pays serious attention to pharmacokinetics and drug sequencing, to develop a novel protocol for treating pancreatic cancer, called “GTX” (G is for Gemzar).

www.fda.gov/cder/foi/l...

So, there is precedent for granting highly toxic chemo drugs with questionable efficacy marketing clearance, and as physicians become familiar with them, there’s a good chance someone will find a way to harness the drug to a particular protocol to help the victims of these dreaded diseases even more. This is a dynamic business, subject to the winds of personnel change and philosophy. But looking back might be instructive – after all, isn’t that why we have historians?

2007 May 15 07:44 PM