A bogus 27 page paper is being aggressively sent around wall street, and the medical, scientific regulatory and legal community, asking people to contact the FDA and the CMS. The cover letter touts the nonsense that they are scared to voice their concerns publicly. Feigning their safety fears is the same ploy they used last time, hiring bodyguards, at the taxpayers expense, fabricating non-existent threats, while no police reports ever turned up. This time we are determined to get to the bottom of it.

provenge-approval-fud.pdf

Their poor argument about the Phase III trial is dispelled here by Provenge advocate Ocyan:

This was a serious piece of work to support an argument that Dr. Hussain put up during the 2007 AC meeting when she said that the placebo protocol might have been active and could hurt patients. At that time, she gave no explanation of how that could be the case. Now, the argument is that it is immuno-depletion.

The basic idea is that a large number of immune cells were taken from a patient in a leukapheresis procedure. If a patient was on the treatment arm, he would get most of them back on reinfusion. However, if a patient was on the control arm, he only got back less than a third of what was taken during the leukapheresis procedure. Therefore, the immune system of a placebo patient was suppressed. That is called immuno-depletion.

The immuno-depletion attack on Provenge goes like this. Because of immuno-depletion,the placebo protocol could harm patients, especially older ones so that they could not recover and died early. In turn, because of this, a survival benefit was seen in the trials of Provenge even though Provenge might not have done anything for patients. That is, the treatment arms of D9901, D9902a and IMPACT were the true placebo arms while the control arms were giving a poison to patients.

The best evidence against this immuno-depletion hypothesis is on page 40 of the FDA Clinical Review where the survival curves for patients taking APC8015F (Frovenge), patients not taking it and treated patients were plotted on the same chart. The curve for APC8015F more or less overlaid the treatment curve, meaning that the survival profile of APC8015F patients was similar or only slightly worse than that of Provenge patients.

Now, the APC8015F patients, of course, underwent immuno-depletion at randomization and did not get back the frozen blood months later. Due to the long elapsed time, the return of this blood could not have done anything to alleviate immuno-depletion. Thus, if immuno-depletion did hurt patients, the APC8015F patients should have died much earlier than the Provenge patients. Yet, that is not the case as seen in the survival curves!

So the conclusion must be that immuno-depletion is an interesting hypothesis but the existing data have shown that it is false.

We would like to add that the FDA approved Provenge! Here is their summary statement:

Regulatory history:

Dendreon Corporation submitted biologics license application 125197 on November 9, 2006 to request approval of sipuleucel-T, an autologous cellular immunotherapy. A Complete Response (CR) letter was issued by FDA to Dendreon on May 8, 2007. This letter requested additional information regarding the manufacturing quality and controls and the clinical effectiveness of sipuleucel-T.

provenge-approval-fud.pdf

A randomized, double-blind, placebo-controlled, Phase 3 study (D9902B) with overall survival as the primary endpoint was ongoing in 2007 when the CR letter was issued. This study has been completed and confirmed the clinical effectiveness of the product. In D9902B, sipuleucel-T extended median survival of men with metastatic, castrate resistant prostate cancer by 4.1 months. The CMC issues noted in the 2007 CR letter were resolved by the sponsor in amendments to the BLA and were confirmed during a second pre-licensure inspection conducted in 2010.

http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM213114.pdf

Popularity: 99%

Tags: Care To Live, CareToLive, Howard Scher, Immunotherapy, Kerry M. Donahue, maha hussain, Prostate Cancer, provenge dendreon, Richard Pazdur

This entry was posted on Thursday, July 15th, 2010 at 9:09 am and is filed under The Cause, The Dysfunctional FDA. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.