DISQUS

Robert Erwin · 2 years ago

Congratulations on an excellent discussion of the complex issues surrounding evidence-based medicine. We are a cancer patient advocacy organization focused on experimental medicine, clinical trials enrollment, and issues in drug approval. Unfortunately, we are one of the few advocacy groups that publicly opposed premature approval of Provenge after the FDA Advisory Committee vote. We believe in aggressive pursuit of effective therapy, but we do not advocate false hope.

Unfortunately, as promising as research on cancer vaccines seems to be in general, Dendreon has not yet provided convincing evidence that Provenge is effective for the medical indication for which the company sought FDA marketing approval. The burden of proof is on Dendreon to prove that Provenge works, not just to provide a basis for hope that it works. If they do this, they will have earned their future profits from cancer vaccine success, but not before.

Your thoughtful article is a good, pro-patient perspective on this frustrating problem. Keep up the good work.

Robert Erwin
President
Marti Nelson Cancer Foundation

James Hadland · 2 years ago

First of all, what have the latest investigative efforts revealed about the obviously botched Dendreon approval efforts? Secondly, how important was the "naked shorting of the DNDN stock to the final outcome of the approval? Was there a conflict of interest for Scher or Hussain or were their opinions pure? I've heard this conflict is urology vs. radiology and money that flows with the right to be considered the best treatment for prostate cancer.

David Hamilton · 2 years ago

Thanks for your comment, James. I'm not entirely sure what you're getting at when you refer to the "latest investigative efforts" or the "obviously botched" Dendreon approval; could you be a little more specific? As for stock shorting, I'm sure you know that it's a fact of life in biotech, where binary events like an approval decision draw shorts like flies whenever the outcome is in doubt. (Don't forget that the losses shorts can take are effectively unlimited -- it all depends on how much the stock bounces up when they're wrong.)

In general I tend to distrust conspiracy theories unless there's some solid evidence, and so far I've seen none regarding conflicts of interest where Scher or Hussain were concerned. (Purity is probably an unattainable standard, though.) Besides, the ultimate decision rested with the FDA; at the end of the day, advisory panel members are just that -- advisors.

Tony F · 2 years ago

David, Thank You! for your article on the FDA, Scher/Hussain and Provenge. I believe it's good to bring this situation into the public domain.

I'd like to comment:
1. While it's been reported in the press that Scher/Hussain have received alleged threats--including from Scher via email, I have yet to see where such clearly illegal actions have merited a report to the police or other law enforcement. Emails are easily traceable and anyone who may have made written threats should be tracked down and prosecuted to the full extent of the law. Such dastardly actions by individuals of threating people because they don't like what action those threatened took should not be condoned in any form...

So, where's the police reports?

2. You say you "distrust conspiracy theories unless there's some solid evidence".... How about these?

Scher reported only 3 COI's to the FDA per his filing in late February available at the FDA website which appears to be composed of ownership of 1 stock and 2 competing industry interest.

Internet research shows the following for Scher thus far:

1. NOVACEA: grants & research support; STUDY CHAIR of DN-101; Direct competitor to Provenge

2. GPB BIOTECH: financial conflict of interest per Scher in MedPage

3. PHARMION: financial conflict of interest per Scher in MedPage

4. SANOFI-AVENTIS: grants & research support

5. BRISTOL MYERS SQUIBB: consultant, grants & research

6. MILLENNIUM PHARMCEUTICALS: grant of research support

7. COUGAR BIOTECHNOLOGY: principal investigator; advisory board;

8. INNOVIVE PHARMACEUTICALS: principal investigator

9. INFINITY PHARMACEUTICALS: principal investigator

10. BIOGEN-IDEC: jointly held stock with spouse

11. PFIZER: jointly held stock with spouse

12. GENTA: scientific advisory board (as of March 6, 2007; since removed from web, but cached)

13. DEPARTMENT of DEFENSE: Principal Investigator PC Clinical Trials-P1 and P2

14. PROQUEST INVESTMENTS: consultant, scientific advisory board; Limited Partner FINANCIAL interest

15. MEDIVATION, INC: principal investigator MDV3100

16. AMBRILIA BIOPHARMA INC: Principal Investigator PCK3145, Phase I/II

There appears to be a significant and disturbing difference between his 3 disclosures to the FDA and the alleged 16 COI's found so far on the internet. It seems incomprehensible for someone with the training and education Scher has to "forget" so many apparent COIs… that is simply beyond all reasonableness and suggests intentional dishonesty or deceit.

Even more disturbing is the FDA's Office of Inspector General and others at the FDA to whom this information has been supplied and their apparent failure to investigate these charges that Scher has more COI's than he disclosed to them. When such information is provided and such allegations of potential federal law violation is involved, any ordinary citizen has the right to expect our government to investigate such allegations timely and thoroughly.

As a "temporary government employee" at the FDA, he is obligated, under Federal law, to provide full and complete disclosure. If he didn't, he may have the potential for liability for law violation(s) as well as for providing false data to the FDA under which he secured a waiver in order to participate on the Provenge AC meeting March 29th.

Advocates for cancer victims will Rally at the Washington FDA office on Sept 18th @ 10 a.m.--info is available at http://www.caretolive.com

Please come support cancer victims and I trust you'll delve further into allegations against Scher and Hussain and their COIs; their leaked CONFIDENTIAL letters to the FDA protesting the apparent approval of Provenge post-AC meeting that appeared in "The Cancer Letter"; and the most unusual actions taken post AC to continue to publicly protest.

David P. Hamilton · 2 years ago

Tony F, thanks for your comment. On the threats and the existence of police reports, I have nothing to add, although I find it kind of hard to believe that the researchers and their institutions -- I think a Sloan-Kettering spokesperson was quoted in the first NYT piece on the threats -- would have made this all up out of whole cloth. Obviously, peoples' opinions on that subject will differ.

On the conflict of interest question for Scher, I don't know that I have a lot to add beyond what Ed Silverman put together here. I'm pretty sure you saw Ed's post, as it looks like you made much the same comment over there. I do agree that it looks fishy, and it's worrying that no one in a position to provide answers is is actually doing so at the moment.

Generally speaking, though, I'd make two points about conflicts. First is the simple one that academic medicine is so tightly intertwined with industry these days that barring anyone with commercial ties from sitting on advisory panels would depopulate the committess. I don't think that makes conflict waivers right, but whatever solution we find to the problem has to grapple with the fact that much of the academic medical profession has some ties to the pharma/biotech industry.

Second is a question back at you: What would actually constitute a conflict on the Provenge panel? People have raked Scher over the coals for his associations with Novacea and Sanofi-Aventis, but it's far from clear to me that the drugs those companies sell or are developing for prostate cancer would actually compete directly against Provenge in any case. Novacea, for instance, lists Provenge in its most recent 10-K as a drug that might be used in combination with Taxotere, which means it might also be used in combination with Asentar.

In other words, it's not entirely clear to me that these drugs are necessarily direct competitors to Provenge, since they're not active immunotherapies. To put the question another way, is Avastin a competitor to Provenge? The Genentech drug is in a phase III test against hormone-refractory prostate cancer, but it was also tested in combination with Provenge. Would an academic who consulted for Genentech be biased against Provenge in your eyes?

I don't bring this up because I have hard-and-fast answers to these questions, but I do think people often oversimplify the issues at stake, and that it's worth thinking the issues a little more carefully.

Paul Haider · 2 years ago

David,
I understand your hesitation believing the assertions regarding Dr. Scher’s conflicts of interest as it may relate to his inappropriate (and perhaps criminal) participation in the recent advisory panel for Dendreon's Provenge. Dr. Howard Scher was not only a dissenting voter against the approval of Provenge, but his over the top crusade against Provenge approval was inappropriate and, I believe, due to his huge conflicts of interest that were not adequately disclosed or considered by the FDA. I would like to provide you with some greater detail of Dr. Scher’s conflicts of public and personal interest.

As you know, Provenge received an FDA fast track designation and was brought before the FDA’s own advisory committee. Provenge received a positive 17-0 vote for safety and a positive 13-4 vote demonstrating efficacy. In an unprecedented reversal by the FDA, Provenge was issued an approvable letter from the FDA instead of being granted immediate marketing approval.

I believe that many of the details below will be news not only to you, but also to the FDA and the prostate cancer community. I am particularly concerned about the lack of separation between Dr. Howard Scher, a Government employee for the Center for Drug Evaluation and Research, and his participation in Dendreon's advisory panel and his financial interests in Novacea, Proquest Investments and the Prostate Cancer Foundation.
What is significant here is the amount of control and influence that Michael Milken possesses over the prostate cancer community and Dr. Howard Scher’s long and close professional relationship to Michael Milken and Dr. Scher’s authority and position within the FDA.

The Prostate Cancer Foundation, founded by Michael Milken, “the Junk Bond King”, in 1993, is one of the largest sources of prostate cancer research funding behind NCI’s Specialized Program of Research Excellence (SPORE) and the Department of Defense’s Prostate Cancer Research Program (PCRP). The Prostate Cancer Foundation has raised over $288 million dollars for prostate cancer research funding since its inception. Dr. Howard Scher has disclosed that he has received material financial support from the Prostate Cancer Foundation and is one of eleven Prostate Cancer Foundation consortium members who review new drugs and determine Prostate Cancer Foundation grants to be awarded. Dr. Howard Soule is Chief Science Officer to the Prostate Cancer Foundation and a ProQuest Investments scientific advisor to the investment company (please see footnote 1). Dr. Jonathan Simons, the President of Prostate Cancer Foundation is also scientific advisor to ProQuest Investments (please see footnote 1). Jay Moorin is a Founding Partner of ProQuest Investments and a board member to Novacea (please see footnote 4). It seems clear that ProQuest Investments operates as an extension of the Prostate Cancer Foundation and Michael Milken. Additionally, half of Michael Milken's Prostate Cancer Foundation consortium members are DOD PCRP consortium members.

Proquest Investments is a $1 billion venture capital fund that was started in 1998, in large part by Michael Milken, the “Junk Bond King”, with a specific focus on prostate cancer (please see footnote 2). Proquest Investments (and its principals) are major shareholders of Novacea. As with the Prostate Cancer Foundation, Dr. Scher has an instrumental role at ProQuest Investments. Dr. Howard Scher is a scientific advisor for and has been granted an ownership interest in Proquest Investments (please see footnote 1). There are roughly 23 million shares outstanding in Novacea. According to SEC documents filed May 15, 2006, Proquest Investments (or it’s principals) appear to own a major stake in Novacea, a company with a $220 million market capitalization. Below is a table that details ownership in Novacea by Proquest Investments (or its principals).

As of May 15th, 2006
Owner Shares
ProQuest Investments II, L.P. 1,779,767
ProQuest Investments II Advisors Fund, L.P 75,508
ProQuest Associates II LLC 1,855,275
Jay Moorin 1,910,988
Alain Schreiber 1,855,275

http://tinyurl.com/2sgpgf

Dr. Howard Scher is the lead investigator of their phase III clinical trial for Asentar, an oral treatment for prostate cancer and a direct competitor of Provenge for AIPC patients. Additionally, Dr. Scher is a Novacea advisory board member. As per Novacea’s form 10-K filed with the SEC in April 2007, Novacea’s ability to commercialize Asentar would suffer if marketing approval of Provenge for AIPC were granted. On May 30th, less than 3 weeks after Dendreon was denied immediate marketing approval for Provenge by the FDA, Schering-Plough and Novacea entered into a worldwide development and commercialization agreement for Asentar worth over $450 million plus royalties if all milestones are met as anticipated. Novacea will receive an upfront payment of $60 million, including $35 million as reimbursement for past research and development expenses, a license fee of $25 million, as well as a commitment by Schering-Plough to purchase $12 million of Novacea common stock at a predetermined price within ten days of the closing. Additionally, the agreement provides Novacea with potential pre-commercial milestone payments of up to $380 million, and tiered royalties on worldwide sales of Asentar.

Howard Scher not only reaps large benefits from his consortium activities reviewing the newest research in prostate cancer, but also compensation for conducting clinical trials for such investments, consulting for such investments, and compensation for sitting on Proquest Investment's scientific advisory board recommending such investments. I suspect Dr. Howard Scher earns far more from these professional relationships than any salary he may draw from the FDA. I think I have highlighted significant examples above of Dr. Scher's, conflicts of interest and how Dr. Scher, Proquest Investments and Michael Milken appear to benefit and profit from inside information.

There appears to be a related party factor that calls into question Dr. Scher's true independence as a FDA panel doctor. With such high powered contacts and Dr. Scher's unmatched power and influence, is there really a level playing field for anyone that doesn't meet Dr. Scher's approval, or which Dr. Scher, Proquest Investments (or its principals) does not have a financial interest in? This is an assault on the trustworthiness of the FDA, the SEC and the financial markets in general.

I have highlighted Dr. Scher’s connection to a $1 billion venture capital fund and a long history to Michael Milken. On top of his close professional relationship to these 2 huge financial titans, his wife’s cousin, Barry Lafer, operates a $200 million offshore hedge fund (Lafer Equities).

There appears to be a certain quid pro quo as it relates to Dr. Howard Scher and his professional involvement with Prostate Cancer Foundation and Proquest Investments (and its principals). Often these are not public companies and Dr. Scher's financial interests, those of Proquest Investments or Michael Milken are not publicly available. Much of these conflicts in ownership do not appear in the public domain until years later when the company files registration statements with the SEC to go public or is perhaps is acquired by a public company. Proquest Investments is a venture capital fund that is not transparent like a common mutual fund and the Prostate Cancer Foundation is a private foundation.

A request for a Conflict of Interest Waiver was requested by Dr. William Freas, Director of Scientific Advisors and Consultants for CBER, on February 5, 2007. The request was concurred by Vince Tolino, Director of Ethics and Integrity, on February 26, 2007. On March 8, 2007, Dr. Howard Scher was granted a waiver by Dr. Randall Lutter to participate in Dendreon's FDA advisory panel for Provenge because an individual with lesser conflicts of interest was unavailable. I don't understand how the need for Howard Scher's individual services could outweigh the above demonstrated conflict of interest created by the financial interest attributable to Howard Scher. I can't imagine an individual participant with more financial conflicts of interests sitting on the FDA advisory panel for Provenge. It is my fear that Dr. Scher's financial interests have come before the best interests of terminal AIPC patients.

http://www.fda.gov/OHRMS/DOCKETS/AC/07/waivers/...

Can there be any question that Dendreon's FDA determination of Provenge was manipulated? 13 out of 17 of the FDA's own experts (chosen with bias) agreed that Dendreon had provided enough evidence of effectiveness to approve it. Historically, the FDA has never decided counter to an advisory committee recommendation for marketing approval for a terminal indication. The FDA’s determination counter to the advisory committee’s recommendation to grant immediate marketing approval for Provenge was unprecedented.

Dendreon is on the SEC’s regulation SHO threshold security list and continues to this day to be heavily shorted. Roughly half of the entire float in Dendreon stock is short. The short interest in Dendreon actually increased 50 percent pursuant to the positive recommendation of the Provenge advisory committee meeting. This response by investors is completely illogical unless somebody knew the outcome in advance. How else can anybody explain the means motive and method to this fact? (please see footnote 3)

Huge financial interests are at stake and the positive outcome of a Provenge application could have dire consequences for those who have a short interest in Dendreon stock. Furthermore, Dr. Howard Scher's partners, Michael Milken and Proquest Investments, have an even larger financial interest in seeing Provenge not approved for terminal AIPC patients. The FDA subjected the terminally ill AIPC patients to more suffering whereby a few would benefit financially.

A full investigation into the matter of corruption within the FDA, and in particular, in the egregious handling of the matter pertaining to the consideration for approval of Dendreon’s Provenge for prostate cancer is needed. Commissioner Andrew von Eschenbach of the Food and Drug Administation was appointed in the aftermath of Commissioner Crawford's unintentional failure himself to disclose his own financial holdings. I suspect there is much greater detail that is just not available in the public domain.

Dr. Howard Scher, as an employee of the FDA, has been granted a level of public trust and the stewardship of such a position demands the highest levels of ethical and moral conduct. Voting on and participating in an FDA advisory meeting in order to determine which drugs receive FDA marketing approval in which you play a decisive role in and in which you have a financial interest in (or counter interest in), is contrary to unbiased public concern and counter to the fiduciary duty Dr. Scher accepted as a special government employee and FDA panel advisor. Dr. Scher’s participation in the Provenge advisory panel is akin to a defendant's own sibling participating on a jury resulting in a hung jury decision. Knowing of Dr. Scher’s close professional relationship to ProQuest Investments, how is the public to believe that the FDA made the correct decision? Surely you can see the travesty of his participation in this matter. Such conflicts of public and personal interest jeopardize the legitimacy of one proclaiming to act on behalf of the public’s best interests.

The fact that Dr. Howard Scher sits on an advisory board to ProQuest Investments and has been granted an ownership position in ProQuest Investments, a $1 billion venture capital fund which has a major financial ownership stake in Novacea, a direct competitor to Provenge, and is allowed to participate in and vote on marketing approval of Provenge is unacceptable ethically. Furthermore, Dr. Scher’s apparent over the top crusade to deny this choice to terminally ill patients for what appears to be financial gain is immoral in light of the lack of treatment options available to terminally ill androgen-independent prostate cancer (AIPC) patients and when considering the undeniable survival benefit demonstrated in combination with Taxotere, the only FDA approved treatment for AIPC.

The survival data shows that the patients that received Provenge had longer median survival (4.5 months) than that reported for Taxotere therapy, without having to endure 7 months of infusion therapy and coping with the poisonous toxic side effects related to Taxotere infusion. In support of its efficacy, a direct correlation between Provenge induction of immune response and survival benefit was also demonstrated in these patients. Most impressively, the data analysis also shows that when Provenge treated patients were subsequently treated with Taxotere, their median survival almost doubled (from 20 months to 35 months). This is compelling survival data further supporting the efficacy of Provenge for hormone refractory prostate cancer. In comparison, Taxotere increases median survival by only 2-3 months. This increase in survival is so dramatic and remarkable, it could not have been due to a random chance. This clearly shows that Provenge is effective at extending overall survival from AIPC beyond any reasonable doubt. This is amazing data.

Provenge received an overwhelming vote of support from the advisory committee and recommended immediate marketing approval be granted. Both Dr. Howard Scher and Dr. Maha Hussain, each of whom voted in the minority and are very powerful members of the oncology community, launched an unprecedented PR campaign accusing those in the majority of incompetence and naiveté in matters relating to cancer products. The arrogance of this campaign overlooked the notion that survival data from Provenge may be qualitatively different from, and may need to be judged by different criteria than, survival data from chemotherapy drugs (as recognized in a July 1st National Cancer Institute research report by Jeffrey Schlom, Ph.D., chief of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute).

There must be standards to public duty and there must be accountability and consequences for failure to meet the necessary high standards. Maintaining the integrity and dignity of the FDA is essential for maintaining high levels of public confidence in our institutions of government.

Footnotes:

1. http://proquestvc.com/scienceadvisory.asp
2. http://tinyurl.com/2w86uo
3. http://www.nasdaqtrader.com/aspx/regsho.aspx
4. http://tinyurl.com/2lfjrz

Paul Haider · 2 years ago

David: I understand your hesitation believing the assertions regarding Dr. Scher’s conflicts of interest as it may relate to his inappropriate (and perhaps criminal) participation in the recent advisory panel for Dendreon's Provenge. I would like to provide you with some greater detail of Dr. Scher’s conflicts of public and personal interest. Dr. Howard Scher was not only a dissenting voter against the approval of Provenge, but his over the top crusade against Provenge approval was inappropriate and, I believe, due to his huge conflicts of interest that were not adequately disclosed or considered by the FDA.

As you know, Provenge received an FDA fast track designation and was brought before the FDA’s own advisory committee. Provenge received a positive 17-0 vote for safety and a positive 13-4 vote demonstrating efficacy. In an unprecedented reversal by the FDA, Provenge was issued an approvable letter from the FDA instead of being granted immediate marketing approval.

I believe that many of the details below will be news not only to you, but also to the FDA and the prostate cancer community. I am particularly concerned about the lack of separation between Dr. Howard Scher, a Government employee for the Center for Drug Evaluation and Research, and his participation in Dendreon's advisory panel and his financial interests in Novacea, ProQuest Investments and the Prostate Cancer Foundation.

What is significant here is the amount of control and influence that Michael Milken possesses over the prostate cancer community, Dr. Howard Scher’s long and close professional relationship to Michael Milken and Dr. Scher’s authority and position within the FDA.

ProQuest Investments is a $1 billion venture capital fund that was started in 1998, in large part by Michael Milken, the “Junk Bond King”, with a specific focus on prostate cancer (please see footnote 2). ProQuest Investments (and its principals) are major shareholders of Novacea. Dr. Scher has an instrumental role at ProQuest Investments as a scientific advisor to the investment fund and has been granted an ownership interest in ProQuest Investments (please see footnote 1). There are roughly 23 million shares outstanding in Novacea. According to SEC documents filed May 15, 2006, ProQuest Investments (or it’s principals) appear to own a major stake in Novacea, a company with a $220 million market capitalization. Below is a table that details ownership in Novacea by ProQuest Investments (or its principals).

As of May 15th, 2006
Owner Shares
ProQuest Investments II, L.P. 1,779,767
ProQuest Investments II Advisors Fund, L.P 75,508
ProQuest Associates II LLC 1,855,275
Jay Moorin 1,910,988
Alain Schreiber 1,855,275

http://tinyurl.com/2sgpgf

The Prostate Cancer Foundation, founded by Michael Milken, “the Junk Bond King”, in 1993, is one of the largest sources of prostate cancer research funding behind NCI’s Specialized Program of Research Excellence (SPORE) and the Department of Defense’s Prostate Cancer Research Program (PCRP). The Prostate Cancer Foundation has raised over $288 million dollars for prostate cancer research funding since its inception. Dr. Howard Scher has disclosed that he has received material financial support from the Prostate Cancer Foundation and as with the ProQuest Investments, has an instrumental role at the Prostate Cancer Foundation as one of eleven Prostate Cancer Foundation consortium members who review new drugs and determine Prostate Cancer Foundation grants to be awarded. Besides Dr. Howard Scher, several other very notable Prostate Cancer Foundation consortium members and officers are key members of ProQuest Investments scientific advisory board as well. Dr. Howard Soule is Chief Science Officer to the Prostate Cancer Foundation and scientific advisor to ProQuest Investments (please see footnote 1). Dr. Jonathan Simons, the President of Prostate Cancer Foundation is also a scientific advisor to ProQuest Investments (please see footnote 1). Jay Moorin is a founding partner of ProQuest Investments and a board member to Novacea (please see footnote 4). It seems clear that ProQuest Investments operates as an extension of the Prostate Cancer Foundation and Michael Milken. Additionally, half of Michael Milken's Prostate Cancer Foundation consortium members are DOD PCRP consortium members.

Dr. Howard Scher is the lead investigator of Novacea's phase III clinical trial for Asentar, an oral treatment for prostate cancer and a direct competitor of Provenge for AIPC patients. Additionally, Dr. Scher is a Novacea advisory board member. As per Novacea’s form 10-K filed with the SEC in April 2007, Novacea’s ability to commercialize Asentar would suffer if marketing approval of Provenge for AIPC were granted. On May 30th, less than 3 weeks after Dendreon was denied immediate marketing approval for Provenge by the FDA, Schering-Plough and Novacea entered into a worldwide development and commercialization agreement for Asentar worth over $450 million plus royalties if all milestones are met as anticipated. Novacea will receive an upfront payment of $60 million, including $35 million as reimbursement for past research and development expenses, a license fee of $25 million, as well as a commitment by Schering-Plough to purchase $12 million of Novacea common stock at a predetermined price within ten days of the closing. Additionally, the agreement provides Novacea with potential pre-commercial milestone payments of up to $380 million, and tiered royalties on worldwide sales of Asentar.

Howard Scher not only reaps large benefits from his consortium activities reviewing the newest research in prostate cancer, but also compensation for conducting clinical trials for such investments, consulting for such investments, and compensation for sitting on ProQuest Investment's scientific advisory board recommending such investments. I suspect Dr. Howard Scher earns far more from these professional relationships than any salary he may draw from the FDA. I think I have highlighted significant examples above of Dr. Scher's, conflicts of interest and how Dr. Scher, ProQuest Investments and Michael Milken appear to benefit and profit from inside information.

There appears to be a related party factor that calls into question Dr. Scher's true independence as a FDA panel doctor. With such high powered contacts and Dr. Scher's unmatched power and influence, is there really a level playing field for anyone that doesn't meet Dr. Scher's approval, or which Dr. Scher, ProQuest Investments (or its principals) does not have a financial interest in? This is an assault on the trustworthiness of the FDA, the SEC and the financial markets in general.

I have highlighted Dr. Scher’s connection to a $1 billion venture capital fund and a long history to Michael Milken. On top of his close professional relationship to these 2 huge financial titans, his wife’s cousin, Barry Lafer, operates a $200 million offshore hedge fund (Lafer Equities).

There appears to be a certain quid pro quo as it relates to Dr. Howard Scher and his professional involvement with Prostate Cancer Foundation and ProQuest Investments (and its principals). Often these are not public companies and Dr. Scher's financial interests, those of ProQuest investments or Michael Milken are not publicly available. Much of these conflicts in ownership do not appear in the public domain until years later when the company files registration statements with the SEC to go public or is perhaps is acquired by a public company. ProQuest Investments is a venture capital fund that is not transparent like a common mutual fund and the Prostate Cancer Foundation is a private foundation.

A request for a Conflict of Interest Waiver was requested by Dr. William Freas, Director of Scientific Advisors and Consultants for CBER, on February 5, 2007. The request was concurred by Vince Tolino, Director of Ethics and Integrity, on February 26, 2007. On March 8, 2007, Dr. Howard Scher was granted a waiver by Dr. Randall Lutter to participate in Dendreon's FDA advisory panel for Provenge because an individual with lesser conflicts of interest was unavailable. I don't understand how the need for Howard Scher's individual services could outweigh the above demonstrated conflict of interest created by the financial interest attributable to Howard Scher. I can't imagine an individual participant with more financial conflicts of interests sitting on the FDA advisory panel for Provenge. It is my fear that Dr. Scher's financial interests have come before the best interests of terminal AIPC patients.

http://www.fda.gov/OHRMS/DOCKETS/AC/07/waivers/...

Can there be any question that Dendreon's FDA determination of Provenge was manipulated? 13 out of 17 of the FDA's own experts (chosen with bias) agreed that Dendreon had provided enough evidence of effectiveness to approve it. Historically, the FDA has never decided counter to an advisory committee recommendation for marketing approval for a terminal indication. The FDA’s determination counter to the advisory committee’s recommendation to grant immediate marketing approval for Provenge was unprecedented.

Dendreon is on the SEC’s regulation SHO threshold security list and continues to this day to be heavily shorted. Roughly half of the entire float in Dendreon stock is short. The short interest in Dendreon actually increased 50 percent pursuant to the positive recommendation of the Provenge advisory committee meeting. This response by investors is completely illogical unless somebody knew the outcome in advance. How else can anybody explain the means motive and method to this fact? (please see footnote 3)

Huge financial interests are at stake and the positive outcome of a Provenge application could have dire consequences for those who have a short interest in Dendreon stock. Furthermore, Dr. Howard Scher's partners, Michael Milken and ProQuest Investments, have an even larger financial interest in seeing Provenge not approved for terminal AIPC patients. The FDA subjected the terminally ill AIPC patients to more suffering whereby a few would benefit financially.

A full investigation into the matter of corruption within the FDA, and in particular, in the egregious handling of the matter pertaining to the consideration for approval of Dendreon’s Provenge for prostate cancer is needed. Commissioner Andrew von Eschenbach of the Food and Drug Administation was appointed in the aftermath of Commissioner Crawford's unintentional failure himself to disclose his own financial holdings. I suspect there is much greater detail that is just not available in the public domain.

Dr. Howard Scher, as an employee of the FDA, has been granted a level of public trust and the stewardship of such a position demands the highest levels of ethical and moral conduct. Voting on and participating in an FDA advisory meeting in order to determine which drugs receive FDA marketing approval in which you play a decisive role in and in which you have a financial interest in (or counter interest in), is contrary to unbiased public concern and counter to the fiduciary duty Dr. Scher accepted as a special government employee and FDA panel advisor. Dr. Scher’s participation in the Provenge advisory panel is akin to a defendant's own sibling participating on a jury resulting in a hung jury decision. Knowing of Dr. Scher’s close professional relationship to ProQuest Investments, how is the public to believe that the FDA made the correct decision? Surely you can see the travesty of his participation in this matter. Such conflicts of public and personal interest jeopardize the legitimacy of one proclaiming to act on behalf of the public’s best interests. The fact that Dr. Howard Scher sits on an advisory board to ProQuest Investments and has been granted an ownership position in ProQuest Investments, a $1 billion venture capital fund which has a major financial ownership stake in Novacea, a direct competitor to Provenge, and is allowed to participate in and vote on marketing approval of Provenge is unacceptable ethically. Furthermore, Dr. Scher’s apparent over the top crusade to deny this choice to terminally ill patients for what appears to be financial gain is immoral in light of the lack of treatment options available to terminally ill androgen-independent prostate cancer (AIPC) patients and when considering the undeniable survival benefit demonstrated in combination with Taxotere, the only FDA approved treatment for AIPC.

The survival data shows that the patients that received Provenge had longer median survival 4.5 months) than that reported for Taxotere therapy, without having to endure 7 months of infusion therapy and coping with the poisonous toxic side effects related to Taxotere infusion. In support of its efficacy, a direct correlation between Provenge induction of immune response and survival benefit was also demonstrated in these patients. Most impressively, the data analysis also shows that when Provenge treated patients were subsequently treated with Taxotere, their median survival almost doubled (from 20 months to 35 months). This is compelling survival data further supporting the efficacy of Provenge for hormone refractory prostate cancer. In comparison, Taxotere increases median survival by only 2-3 months. This increase in survival is so dramatic and remarkable, it could not have been due to a random chance. This clearly shows that Provenge is effective at extending overall survival from AIPC beyond any reasonable doubt. This is amazing data.

Provenge received an overwhelming vote of support from the advisory committee and recommended immediate marketing approval be granted. Both Dr. Howard Scher and Dr. Maha Hussain, each of whom voted in the minority and are very powerful members of the oncology community, launched an unprecedented PR campaign accusing those in the majority of incompetence and naiveté in matters relating to cancer products. The arrogance of this campaign overlooked the notion that survival data from Provenge may be qualitatively different from, and may need to be judged by different criteria than, survival data from chemotherapy drugs (as recognized in a July 1st National Cancer Institute research report by Jeffrey Schlom, Ph.D., chief of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute).

There must be standards to public duty and there must be accountability and consequences for failure to meet the necessary high standards. Maintaining the integrity and dignity of the FDA is essential for maintaining high levels of public confidence in our institutions of government.

Respectfully,
Paul Haider


Footnotes:

1. http://ProQuestvc.com/scienceadvisory.asp
2. http://tinyurl.com/2w86uo
3. http://www.nasdaqtrader.com/aspx/regsho.aspx
4. http://tinyurl.com/2lfjrz

Tony F · 1 year ago

David,

Today is the 1 year anniversary of the FDA Advisory Committee meeting in which Drs. Scher and Hussain participated in the judgment of Provenge and who later, after the most impressive and most positive AC recommendation of Approval or Conditional Approval of Provenge initiated the unprecedented letter writing to persuade the FDA to not approve Provenge.

83 men die daily from prostate cancer.

Since the May 9th FDA delay in any type of approval, 26,894 men have died.

With all the information given you about 9 months ago, have you considered verifying this information and doing a follow up on Provenge?

There is new information out from Dendreon on Provenge and it's revised SPA with the FDA which has shortened by a year.

Any comments?