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In Response to the Reuters Article Featuring Marie Huber's Analysis of the Pivotal Provenge Study

To the editor:

As someone who covers the biotech universe*, I frankly am appalled that Ms. Huber’s writings have attracted the attention they have in the popular and medical media. The Reuters’ article you posted to your site contains significant misleading statements and does a disservice to readers, medical practitioners, and prostate cancer patients alike.

Insight: New Doubts About Prostate-Cancer Vaccine Provenge
(Reuters) Mar 30, 2012 - Prostate cancer vaccine Provenge has long incited passions unlike any other cancer therapy.
read article »

Ms. Huber's specious theory has been and continues to be ridiculed by mainstream immunologists and other scientific thinkers, including none other than Dr. James Gulley, the Director of Clinical Trials at the US National Cancer Institute. As can be seen, for example, in the descriptive material related to Dendreon’s Sipuleucel-T (Provenge) on Wikipedia:

'This theory was brought up at the CMS Advisory Committee Meeting in November 2010. At that meeting, Dr. James Gulley, Director of Clinical Trials at the National Cancer Institute, dismissed it as follows[15]: "The number of white blood cells that were, the proportion of white blood cells that are removed in terms of the total body white blood cell count is around two percent, so it is not a clinically meaningful amount." In addition, a recent retrospective analysis of patients on the control arm of the IMPACT trial[16] showed that those treated with salvaged Provenge many months after disease progression had median survival time 23.8 months which was far better than the 11.6 months seen with the pure placebo patients. The median difference between patients on the control arm treated and untreated with salvaged Provenge was a direct contradiction to the Immunodepletion theory.

[15] "An analysis to quantify the overall survival benefit of Sipuleucel-t accounting for the cross-over in the control arm of the IMPACT study".

'Lastly, the above same analysis of the control arm of the IMPACT trial showed that the recorded median difference of 4.1 months might have been an underestimation due to the longer life of patients treated with salvaged patients. The presentation[16] stated: "Using the RPSFT model, and assuming that APC8015F (salvaged Provenge) was equally effective as PROVENGE, the median overall survival benefit of PROVENGE in the Phase 3 IMPACT trial was estimated to be 7.8 months, had there been no cross-over to APC8015F (HR=0.60, 95% CI: 0.41, 0.95)."'

[16] "NCT00779402: Provenge for the Treatment of Hormone Sensitive Prostate Cancer". US National Institutes of Health.

It must be noted, by the way—and unfortunately, this is either overlooked or ignored by the media—that the Journal of the National Cancer Institute (JNCI) has no relationship whatsoever—NONE—with the United States National Cancer Institute. The JNCI is published by Oxford University Press in England.

As to JNJ’s Zytiga, that drug’s Phase 3 trial was recently stopped because it reached stat sig one of two primary end-points: progression-free survival (PFS). The trial did not reach stat sig on the other primary end point: overall survival (OS). Now, with patients crossing over from the placebo cohort and taking Zytiga, chances are getting slimmer by the day that the trial will reach stat sig on OS. Whether or not Zytiga is approved for pre-chemo PCa patients, then, will depend on the strength of the PFS data and how close the trial comes to achieving stat sig on OS.

Finally, writing in the March 2012 issue of AUA News (p. 42), Dr. Carl A. Olsson had this to say about the paper published by Huber et al. in the JNCI:

“The authors missed the report by Hall et al that “there was no evidence that leukapheresis led to immunodepletion,” citing literature proving that each apheresis removed less than 1% of the total body pool of 1012 lymphocytes and reporting a normal measured cell count after the third apheresis in all men.[3]

“Finally, we are all used to the values of interdisciplinary conferences, which usually combine the experiential qualities of urology, clinical oncology, immunology and other disciplines. However, “healthcare analyst” and “investment management” are talents that appear unseemly in major publications.”

[3] Hall SJ, Klotz L, Pantuck AJ et al: Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. J Urol 2011; 186: 877.

by Theodore J. Cohen, PhD

*Theodore Jerome Cohen, PhD, writes for Seeking Alpha and is a Dendreon Shareholder. He is the author of Death by Wall Street: Rampage of the Bulls. [ed]

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