Patient Action Sign-On Letter

Here’s the text of the letter I emailed to Lanessa Hill this morning (which includes my email to Doctors Witten, Goodman, and Von Eschenbach). I am appalled, disgusted, and very much betrayed by the FDA’s last-second change of heart, or lack of heart.

Lanessa,

Thank you very much for the reply. I’m sure your email box has been very full. I’m pasting below the text of the emails I sent to Doctors Witten, Goodman, and Von Eschenbach. I do understand you can not discuss this further and I do understand the public relations hit Iressa has caused the FDA, but that does not excuse what appears to have been a very last minute change of heart somewhere within the FDA, choosing to be a barrier to further drug development for a great many companies instead of a bridge of hope for patients. The simplest point I can make is this. When the FDA had the chance, back in 2005, to tell sponsor that the data from its two small PIII trials would not be enough, that some data from 9902b would be needed, they did not take the opportunity. Having fully reviewed the safety AND efficacy data of the two trials at THAT time (which has only gotten better as time has passed I understand), the FDA said THIS data ALONE is enough to support your filing. What better could the sponsor have done with the data YOU TOLD THEM was enough? They got a 17-0 safety vote and a 13-4 vote in favor of substantial evidence of efficacy, all this in favor of a new treatment for terminal, end-stage patients with NO real alternatives. And yet, for the FIRST TIME IN HISTORY, FDA overturns an AC vote and chooses to NOT approve and AC endorsed treatment for an end-stage patient group. THAT is what is absolutely stunning and unconscionable. I’m quite sure a better compromise could have been reached to ensure full enrollment of 9902b had that been the desire.

Thank you again for your time and your response. I’m sorry to have learned the FDA has not changed for the better with the addition of Dr. Von Eschenbach.

Sincerely,

Text of letter to Doctors Witten, Goodman, and Von Eschenbach:

Let me share why I have those feelings, and I’ll try to do it quickly, in bullet point form because I do realize you’re busy folks:

When Dendreon filed its BLA with FDA, FDA had the opportunity to say, “no, there is not enough data within these two smaller studies to support your filing, you will need to have data from 9902b if you hope to be approved” and FDA did not say this. FDA said the data set sponsor submitted could be enough for approval, knowing completely the data set contained already.

“A bridge, not a barrier” Have more hollow words ever been spoken?

The FDA has NEVER, to my knowledge, overruled an AC panel in order to NOT approve a drug that the committee recommended for approval that treats end-stage, terminal disease.

The safety vote was 17-0.

The vote that the data, as submitted, ‘demonstrated substantial evidence of efficacy’ was 13-4. And yes, I watched and saw the discussions and heard desires to continuation and tracking of either 9902b and/or the 3000 patient pharmaco-vigilance plan, but it was clear that these were (outside of a few, more conflicted folks) in the vein of 9902b as a Phase IV, post-marketing trial, not as pre-approval.

Given that the data set as submitted in the BLA was deemed by FDA to be enough to support a BLA application and approval, what more could sponsor have done? They received 17-0 safety vote, 13-4 in favor of efficacy, with 4 votes coming from essentially ODAC members with substantial conflicts of many different natures. IF you believe this approach is immunological, and ALL the immunologists voted to support efficacy/approval, how do you justify overturning that AC decision and NOT approving this drug?

How do you justify to the men you’ve just sentenced to death this untenable delay GIVEN that FDA said the data set is enough to support the BLA filing?

To say that the trial did not meet its primary endpoint of TTP even though p-value = .052 is beyond ridiculous. An additional 2 in 1000 chance that the TTP effect was due to chance, given that p-value for survival was .01, and you believe the trial did NOT meet endpoint? .05 is an artificial construct, you understand, and .05000001 is as much a miss and as foolish a FAIL as .052.

The Kaplan-Meir curves EVEN ON TTP, if you look at the slides, are OBVIOUS, assuming you start to look at approximately 10 weeks, after all three infusions have been given. They are separate, distinct, and statistically meaningful at that point, without question.

You make an argument that 2nd trial is not supportive, as p-value moves from .01 to .011. Supportive does not mean ‘better’ it means ‘helps support or defend’. NOT supportive would have been if all patients in second trial acted as placebo patients did, which would have taken p-value above .05. This did NOT happen as patients STRONGLY trended to the same effect as initial trial, thus adding only an additional 1/1000th possibility that efficacy seen was due to chance.

The doctors involved in the study explain why on scan the tumors appear to have progressed, even though when analyzed further it’s clear the body has been attacking tumors from the inside.

In the absence of any real side effects, and given that 9902b could have been measured against the Halabi nomogram, for instance, or against Taxotere effects for measurement purposes, what COMPELLING reason can you give for NOT approving this drug for patients about to die?

34% of men taking Provenge alive at 36 months. 11% placebo alive at 36 months (and ONLY 2 in placebo did NOT receive frozen Provenge!). P-value=.01. One in one hundred odds that the benefit was due to chance and you don’t want patients to have that choice when there are no significant side effects?

There’s so much more, but please help me (and the many men who WILL NOW DIE BECAUSE OF YOUR CHOICE) understand why and how you did what you did and burned the bridge for patients, once again proving the FDA puts ‘process’ before patients. There is no justification that this decision is in the patients’ best interests that I can possibly see, so please help. I truly hope you have a solid rationale for this decision that is not driven by old-school ODAC thinking that has dominated FDA for years and created hundreds of thousands of new victims by its aggressive incompetence. Thank you.