FDA Turns Over Dendreon Documents - Here They Are

When I got back from the Pfizer (PFE) analyst meeting in New York City Wednesday afternoon, I found a treasure trove of PDF documents in one of my inboxes from a couple of Dendreon/Provenge proponents from their Freedom of Information Act request to the Food and Drug Administration.

At first, the FDA said it couldn't find any communications regarding the deliberations over whether to approve the prostate cancer drug.

In a response to the lawyer who filed the request the agency wrote on January 24 of this year that, "After a diligent search, this office has not located any responsive records." But apparently the FDA later discovered that wasn't the case. In a similar letter dated February 26 from the same "Freedom of Information Specialist" at the FDA it states, "...records were located in the Immediate Office of the Commissioner."

Here's what they found (.pdf documents):

* Read Document No. 1
* Read Document No. 2

Most notable to those who are following the Dendreon Dendreon Corp (DNDN)/ Provenge saga are the letters sent to FDA Commissioner Dr. Andrew von Eschenbach by the two influential FDA Advisory Committee members who were among the four panelists who voted against recommending approval of the drug. A congressional committee recently decided not to hold a hearing or launch an investigation into allegations of ethical violations and conflicts of interest against the two doctors.

On April 5 last year, Dr. Howard Scher wrote, "...the (clinical trial) results do not support an approval recommendation." And he argued against the precedent Provenge approval might set: "It also opens the door to the premature approval of drugs based on inconclusive data." His correspondence does not have any kind of letterhead.

But the communication from Dr. Maha Hussein was sent on University of Michigan Health System letterhead. Also last April, she wrote, "...this particular agent (Provenge) did not even meet criteria for its primary endpoint (clinical trial goal)."

Dr. Hussein advocated that the agency wait until an ongoing, larger clinical trial is finished before making a decision. "These questions (about safety and efficacy) will never be answered if the decision regarding this agent is not deferred at this time until all patients are accrued and data are mature," she wrote.

Dendreon says interim results of that study should be available in the second half of this year. If they're robust enough, the company says the FDA has indicated it might approve Provenge based on that early data. If not, the company, prostate cancer patients and the investment community will have to wait another year or two for the full results to come in.

Comments

[MySeekingAlphaID]

Here’s yet another example where the FDA initially either lied or was totally inept…or both.

The evidence finally released shows that von E received Scher’s letter via e-mail and direct through the U.S. mail.

Interestingly, the last letter in the latest transmission from HHS via FOIA is an e-mail from Dr. Scher to Dr. von Eschenbach that includes an e-mail from Dr. Steven Rosenberg (was the communication from Dr. Rosenberg invited by Dr. Scher?) dated April 27, 2007, supporting Dr. Scher. Dr. Rosenberg is in NCI (as are other at least two other government employees already identified as being involved in the development of the infamous "Scher letter" that was leaked to The Cancer Letter). Dr. Rosenberg, in particular, has devoted his life’s work to cancer vaccines, and it’s possible that the approval of Provenge would have pushed his work into the background.

Regardless, it’s interesting that as late as the end of April 2007, a special government employee (Dr. Scher) still was lobbying the FDA commissioner to turn down the approval of Provenge. Dr. Scher could not have mounted such a campaign as a special government employee without the advice, assistance, and support of a regular government employee…it’s just unheard of, and in any event, totaly unexpected for a special government employee who has sat on an advisory committee.

Who is behind the campaign to sink Provenge? Only time will reveal the true identity of the Wizard of Oz...the person behind the curtain, pulling the strings.

Meanwhile, this whole scandal smells worse with every passing day.

The time is long past for a full investigation into Dr. Scher’s (as well as Dr. Hussain’s) activities during and following the Provenge advisory committee meeting.

[bull trout]

Thank you Mike for telling this tale. It looks pretty stinky to me. "after a diligent search" (ooops)

Isn't this the same routine that HRC used when congress requested papers? Could not find them, and then they showed up IN HER OFFICE! Oh my, how things have not changed in DC.

One thing these letters demonstrate is that the majority of the AC's opinions were ignored to listen to these nay-sayers, who because they shouted louder and were supported by insiders at the FDA, won the day. Guess what? Men die every day because of this decision. What could have driven such a decision?

Could it be money? In America?

[cmnman99]

So we have two COI panel members overturning the entire Advisory Panel by a couple of choice letters to the Commissioner. Why even bother with Advisory Panels anyway. Just ask the people with the most to loose if the drug is approved, that would say a lot of time and money!

[User 8136]

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[User 8136]

Dr. Scher and Dr. Hussain are not independent. Simply "follow the money" and anyone will quickly discover these two FDA Advisory Committee members have ties to those with interests that are in direct conflict with the Provenge approval.

Seems to me the bigger story is not the results of Provenge, but the approval process, obvious conflicts of interests involved, and the huge implications that flow from this.....

Surely, a committee member that is found to have a personal conflict of interest, and is vested in the results of an approval/disapproval of any drug, should not be allowed to sit on this this advisory panel and advocate either way. Yes?

With a small amount time and effort, an ambitious investigative reporter could easily pull all the pieces together and have a "career making" story to tell. I'm sure it would be a wild ride, from hedge funds with massive short interests, to multinational drug companies, to back room deal making with those who could influence the outcome. It would be an engaging and eye opening expose'.

Mike Huckman, are you still there? Hello? Hmmm.... maybe 60 minutes or 20/20 will take the initiative breathe some life into this saga and shed the light of truth on this travesty.

[maxbid]

Interesting article, and the reader comments at the end are also very interesting. Be sure to read those. Exactly how I feel. The FDA needs to be overhauled and rebuilt without the special interests.

What gives the FDA the right to decide if people should die every day of cancer? In the USA alone, 83 men die every day of prostate cancer. Not a week or a month or a year, but everyday for 365 days a year!

Why can't we have a "for trial use only" where patients can sign a waiver (letting the FDA off the hook) and go ahead and get the vaccine? I'll take a chance any day on a vaccine that might keep me alive rather than die. Good grief people, wake up!

Remember, the company Dendreon with the prostate cancer vaccine also has a vaccine for breast cancer.

Put this into your democratic platform: The FDA needs to be overhauled....They're killing hundreds of Americans every day and getting away with it.

[User 161198]

It was clear that Provenge failed its primary endpoint in the predefined pivotal phase 3 protocol. If this owuld have been approved, it would have set a major precedent in the history of US regulatory and sceintific standards!!! Once predefined primary endpoint fails, every other post-hoc analysis would be considered data mining or fraud!!

[kyoto27]

Q to User 161198:

Provenge had a p-value of .052.
Are you really suggesting that a p-value of .052 is showing the treatment ‘failed to slow progression?’ To the contrary, a p-value of .052 clearly showed that the treatment slowed progression of symptoms of the disease and, in fact, most biostatisticians would call a p=0.052 level of significance “nominally statistically significant.”

Why the FDA did not think so in this case is unknown. Especially when you add the stellar survival log-rank p = .01 for D9901 (which was on the entire trial, not some subgroup) the FDA decision becomes what in fact it really was –unprecedented in this terminal disease setting.

And let’s not forget that the FDA, by virtue of its own revised trial design guidance, has demoted the importance of traditional markers such as TTP, subordinating them to overall survival. Nonetheless, Provenge naysayers continue to trot out TTP like a champion mare when it suits them, knowing that it is an unacceptable endpoint for making an approval decision.

I’ll let the FDA have the last word:

“When a study fails to meet its primary endpoints, there's no alpha left for other endpoints analysis. So literally, means from pure statistical point of view, the difference in other endpoints should not be considered statistically significant. Therefore, it is very difficult to interpret the hypothesis test result for overall survival in Study 1.

So if overall survival is one of the many unspecified endpoints, under testing it is very possible that a p-value of 0.01 was observed just by chance. However, survival is not one of the many, many endpoints that can be randomly selected for testing. Survival is a preferred endpoint for cancer trial. As Dendreon and Dr. Liu just mentioned, this endpoint is reliable, clinically meaningful. This is why we are here seeking advice from the (Provenge) advisory committee meeting.”

Dr. Bo-Guang Zhen, Ph.D (Division of Biostatistics, FDA )

[r.willett]

These two people , I,am trying to keep this clean !! Have two much POWER, or they think their the ALMIGHTY. Why is it the RICH have to go to a foreign country for treatment ??? You donate to different medical searches, but need a PASSPORT for HELP. I think these people have a background for GREED,& they haven,t got paid YET !!!