Dendreon, Provenge And Conflicts Of Interest
26 CommentsBy Ed Silverman // July 20th, 2007 // 4:36 pm
At the center of the red-hot controversy over Provenge, the prostate-cancer vaccine that has provoked passionate debate among patients and investors, is Howard Scher, a prominent oncologist at Memorial Sloan-Kettering Cancer Center in New York.
Scher sat on an FDA advisory panel that, earlier this year, unexpectedly endorsed Dendreon’s product. But Scher and one other doc weren’t fully convinced, and wrote the agency about concerns they had with Provenge trials, triggering an FDA delay. The stock, meanwhile, was gyrating. And cancer patients and their families were outraged, prompting protests, bodyguards for the docs at a recent cancer meeting and, of course, Internet missives.
Some missives have focused on Scher’s alleged conflicts of interest. He was granted a waiver by the FDA before the hearing, but the Internet is filled with other alleged conflicts not referenced on the form. (That’s Scher to the right).
One allegation involves Scher’s association with ProQuest, a venture capital firm, where he is a scientific advisory board member. As it turns out, ProQuest’s chairman, Jay Moorin, is listed as a board member of Novacea, another company developing a different prostate cancer treatment. And ProQuest holds a chunk of Novacea stock.
So we asked the FDA if the agency was aware of this connection and, if not, whether it would have liked the info prior to the meeting. This is what the FDA wrote us…..
….”The FDA screens advisory committee members in relation to an upcoming drug or biologic product advisory committee meeting for conflicts of interest by requiring disclosure of the member’s current and past involvement in matters involving the product at issue, competing products, or matters involving other ‘affected firms’ as determined by FDA. For example, if an advisor’s duties as a member of a scientific advisory board included providing advice to that firm on the product or competing product, he or she should report it. If the duties did not involve such advice, the advisor would not be required to report the financial relationship with the firm.”
That’s not exactly a straight answer. Meanwhile, we chatted with a Sloan-Kettering spokeswoman, but Scher never got back to us. Moorin left voice mail saying he generally doesn’t comment to the media, and never responded to our follow-up message. So is this a conflict of interest? For safety’s sake, should it have been reported to the FDA? If the FDA was aware, why didn’t the agency just say so?
So we asked Art Caplan, who heads the Center for BioEthics at the University of Pennsylvania, for his thoughts: “This is something that’s potentially relevant. I can’t imagine the FDA wouldn’t find this of keen interest…In the thick of this controversy, I would say, prima facie, disclosure is going to be very important here, because someone wants a cure and there’s money on the line…It’s clear we should disclose our conflicts and, when controversy erupts, we should also disclose marginal conflicts.
One thing I would add is that part of what we’re seeing here is conflict of interest used as a weapon to discredit or attack someone else. It’s possible this doctor felt he didn’t have a relevant conflict and the connection had nothing else to do with the subject. But it becomes very important to start disclosing, because it’ll be used as a club in the fight. Unfortunately, we haven’t figured out how to evaluate disclosure and so it makes all this sticky.”
Scott
OUTSTANDING piece. Glad you talked with Caplan about it and at least asked MSK and Moorin. Didn’t expect them to answer, but, like the FDA, if the answer were, “He has no conflict and no relationship with ProQuest, etc.” they’d have told you.
SOMEONE needs to keep delving into this story, because Dr. Scher’s failure to report what appears to be a VERY significant conflict is troubling. Why not report it if it’s NOT a big deal?
Of course, the fact that ProQuest’s 8.3% stake in Novacea doubled the day its recent deal with Schering-Plough was announced might have something to do with it. Think that deal was going to be anywhere near as sweet/big if Provenge had already been approved?
Yes, if Asentar is approved, Provenge is not precluded and can get approved fine. But if Provenge were approved first, how hard is it going to be to get people enrolling in trials and taking harsh chemo type drugs that don’t offer half the benefit while delivering way more toxicity? Right, thus the need to not have Provenge approved first…
Dr. M
OF COURSE Dr. Scher’s involvement in Novacea is relevant. HE IS THE LEAD INVESTIGATOR FOR THEIR PHASE III TRIAL OF DN-101, A DIRECT COMPETITOR TO PROVENGE. He said so himself in his letter to the FDA (which was published in The Cancer Letter), when he introduced himself as a lead investigator on DN-101 and complained (falsely) that DN-101 results were as good as Provenge’s. If you want another source, see Novacea’s own press release on the DN-101 trial naming Scher as lead investigator: http://www.psa-rising.com/wiredbird/novacea_0406.html
Tony F
Mr. Silverman,
Your article is one of the few accurate and one of the most genuine and fair articles concerning Scher’s Conflict of Interests (COI’s) for the March 29th Provenge FDA Advisory Committee meeting. On behalf of current and future PCa patients, Thank You! for just presenting the facts alleged by many of Scher’s UNdisclosed COI’s.
As noted from verifiable internet resources, Scher apparently 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 2 stocks and 1 competing industry interest.
Internet research shows the following for Scher thus far:
1. NOVACEA: grants & research support; STUDY CHAIR of DN-101
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
13. PROQUEST INVESTMENTS: consultant, scientific advisory board; Limited Partner FINANCIAL interest
From the FDA’s response to you, it appears that the FDA REQUIRES AC meeting members (including Scher, in this case) to disclose ALL of his COI’s. From their above letter to you, it does not appear they make any other investigation other than what is presented to them by the waiver applicant; it looks like they accept the word of their “temporary government employee” without further verification.
There appears to be a significant and disturbing difference between his 3 disclosures to the FDA and the alleged 13 COI’s found so far on the internet. It seems incomprehensible for someone with the training and education Scher has to “forget” 10 conflicts of interest… 1 MAY be reasonable, but 10 (or possibly more) simply is 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.
Additionally, as a “temporary government employee” for the Federal government, 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.
I’m also pleased to see you mentioned the alleged “threats” Drs. Scher and Hussain reported in both the media and to ASCO where they sought–and obtained–body guards at that meeting. It seems, indeed, strange that no one has reported seeing these allegedly threatening emails or letters first-hand nor has it been reported that either doctor has notified the police or other authorities of such alleged bodily threats against them. Had such threats come via email, it is more than a simple matter for law enforcement to easily track down the alleged perpetrators. Why hasn’t anyone seen these alleged threats and why aren’t law enforcement agencies pursuing them to insure Scher and Hussain’s security? Are they even real?
The true tragedy in the Provenge folly is the 27,050 men–according to the American Cancer Society and the National Institutes of Health–who will succumb to their TERMINAL prostate cancer in the next 12 months alone! It appears interim data will be at least 12 additional months away. In the event it takes the full 2 or 3 years for the complete data to be submitted to the FDA and for the FDA to act, the Death Tally will be between 54,000 and 81,000 men who will die prematurely from the FDA’s current actions.
Is it no wonder patients, families and advocates are making this cause known to media, Congress and the FDA? Such a horrendous death toll, if noted nightly in the media as the Iraq war casualties are, would create a firestorm and clamor from the general public as well for this product to be released to those suffering such TERMINAL cancer.
That is 82 men each and every day, 24 hours per day and 7 days per week.
Provenge satisfied 100% of the 17 voting members (including Scher and Hussain) of the March 29th FDA AC meeting that it is “substantially safe” and 13 of those 17 positively voted that Provenge shows “substantial evidence of efficacy”.
The only FDA approved alternative treatment for these TERMINAL men is Taxetore, a horrible chemotherapy of which 50% or more men refuse to take it because of the horrible side-effects of this treatment and it’s reported that 1 to 1% of those who do take it die from the treatment–not their cancer.
Again, Thank You! for your honesty and integrity in reporting this situation. I trust you’ll continue to look into the allegations being made against Scher and report–either way–to keep your readers appraised of what you find.
Tony F
Typo CORRECTION:
“it’s reported that 1 to 2% of those who do take [Taxetore] die from the treatment–not their cancer.
sam
For the sake of all the men suffering please keep digging in to this story, please
John Quigley
For any of us who read,this is an article worth saving,for
two reasons,no agency of goverment should be so arrogant
it is not acceptable.If in fact conflict of interest is found to be the case here,then heads will likley roll at the FDA.
But more important their are thousands of sick people who
should not be denied this link of hope,so their life for 1 day
or six years can be extended,one can feel this emotion just
thinking about it.Someone who has the power should take a
post haste stand here and get to the bottom of this.Secondly
it speaks the truth about people who can put 2+2 together.
Harry
Just a thank you to Tony F. Very nice post.
Paul Haider
Excellent commentary! I try to live a healthy lifestyle. I exercise, I try to eat well and seldom ever take medication. Having a recognized safe treatment option, like Provenge, that trains my own body’s immune system to fight AIPC as a treatment option is something I would want available to me if I faced death from AIPC. The FDA’s actions will needlessly delay access to recognized safe treatment for 30,000 men annually.
Forsaking survival of terminally ill AIPC patients for financial gain is a moral injustice. Mr. Silverman, what can be done?
Ram Potti
There is a material COI. Even the 10K field by
Novacea explecity states That ” Novacea’s ability to commercialize Asentar would suffer if marketing approval of Provenge for AIPC were granted.”
In the case of Novacea, 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. Proquest Investments (and its principals) are major shareholders of Novacea. Proquest Investments and it’s principals own roughly 1/3 of all the outstanding stock in Novacea, a company with a $220 million market capitalization,
Thanks
Ram
Jackie Norman
Thanks for publishing this article. The facts are hard to come by as everyone has tried to cover them up. Please keep up the good work. You have my support and appreciation.
Melody
Mr. Silverman,
Thanks for the most factual article on the Provenge saga to date. I relish the day when this story is blown wide opened. You are well on your way, Mr. Silverman.
Thanks to Tony F’s eloquent post, I will only address the ASCO/bodyguards’ angle. My husband and I organized the Chicago/ASCO protest on June 2, 2007. He is a physician and I am a registered nurse. There were 13 other participants
who were prostate cancer survivors, family members of prostate cancer survivors/victims, breast cancer survivor, an author, veterans, doctors, nurses, and other professionals. I can assure you, we made threats to no one and were not there to threaten anyone. In fact, we were made aware of the threats when a New York Times reporter called our home the following Sunday to obtain a statement. If the bodyguards were hired for our benefit, they
were a complete waste of money. We are in the business of saving lives, not threatening lives.
Thanks again and keep applying pressure to this profusely bleeding wound.
Mike Flynn
Thank you for being the only one in the press that seems willing to address this outrageous COI!
I hope your article begins a flood of attention to this corruption.
Tom Smith
Do you think the Novacia/Schering Plough deal would have happened if Provenge received full approval???? IMHO no it would not have! That’s the reason Scher campaigned to have a CR letter granted for Provenge! This guy has very serious coi’s and if the FDA.SEC,DOJ, are not investigating this they are either blind/incompetent or corrupt! Thanks for the great article I hope you dig deeper into this story. Proquest,Scher, Novacia,Hussain, Hedge Funds short dndn all need to be investigated! It funny how the short interest increased by ~ 10 million shares after the AC committee voted 13-4 and 17-0 to approve Provenge. Now imho someone leaked something to these short sellers after all who in their right mind would short more shares after a very positive AC vote…….unless you had inside info that only a CR was to be granted! IMHO something does indeed smell in the offices of the FDA!! Shame on them I really don’t know how they sleep at night!
jason
I shorted it when I saw that some analysts had projected $1 billion in sales. I don’t practice in this area, but did have ideas of competing products such as hormonal therapy and the business they did. Seeing the trials and showing 5 a median of 4.5 months survival benefit, there is no way I saw this as a $1 billion dollar product.
There could certainly be something fishy, but I don’t think that is entirely d/t the COI. I saw a problem with analyst projections right off the bat.
Cliffhucker
Fantastic Ed!
You have written more relevant and meanigfull content than any other “journalist” to date on this subject of Provenge.
The funny thing is you have only touched upon the tip of the iceberg that is the Provenge Debacle.
Dendreon (and many other small biotechs) have been getting screwed over for years by Wall Street and the powerful Hedge Funds which seem to be above the law of the SEC. (Is the SEC a Hedge Fund?)
I certainly hope that you continue to melt this filthy iceberg so that not only Scher with his alleged Conflicts Of Interest (COI’s) but also those who are responisble for letting him get away with it, those who are pulling the strings are exposed for their wrong doings.
Keep keeping it real Ed
Rollo22
Dear Mr. Silverman,
I fully support you in the effort to shed light on the FDA process.
I am convinced that the opaqueness of this process and especially the
waiving of the COI by the FDA Internal Controller, is one of the main reasons in the chain of events that ultimately lead to the rejection of Provenge.
In this particular case the real COI of Sher and Hussain was much more extensive than what was declared and waived.
Many thanks for your efforts in this matter.
Roberto F.
Italy
The Dude Abides
Jason, you got lucky with your trade because you shorted Dendreon for the wrong reasons. Provenge would not compete with hormone therapy, as the treatment indication that Dendreon is going for is hormone-refractory prostate cancer. In other words, the stage of prostate cancer where it becomes terminal because hormone therapy no longer works. There are probably at least 100,000 people in the US currently who are at this stage of PCa, with another 50,000 whose PCa becomes hormone refractory each year. At $40K per treatment, that’s a pretty big market.
John Greenwood
Thank you for taking time to investigate this most important issue. The story was well done.
Craig Payne
Mr. Silverman…
Excellent coverage. Please consider a follow-up article further delving into the particulars of the Provenge “story” and the morally unjustified FDA decision to deny a clearly Safe and Superior treatment from those terminal patients with no acceptable alternative.
Some recipients of Provenge are alive and well over 6 years later. For a certain percentage of those with end-stage prostate cancer, the FDA’s decision will not only result in needlessly premature death, but needless death period!
Something is terribly wrong at the highest echelons of the FDA.
Thankyou, from every prostate cancer patient in America…but especially from those who have end-stage disease.
Michael Higgins
If COI’s can influence the outcome on a drug like Provenge, then how many more drugs meet their demise due to competing mercenary interests. The president’s appointments in his two terms of office continue to disapoint. At the FDA, first Lester Crawford was corrupt … and now we have an ineffectual Von Eschenbach (that is the best we can say about him at this point). FEMA and the disaster in New Orleans has shock value and hence greater publicity. However, the cost in lives due to the FDA is much much greater.
Tom Smith
Hey SEC WAKE UP!!!!! Hey DOJ WAKE UP!!!! Men are dying from AIPC earlier than need be! Why are you not looking into this travesty??? SCHER/Novacia-Schering Plough deal! Scher and Proquest which holds large position in Novacia and -0- shares of DNDN!!! Over ~30K dead from PC since Black Wed. 5/9/07
Paul Haider
Dr. Scher has been granted a level of public trust and the stewardship of such 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 he has a financial interest in (or counter interest in), is contrary to unbiased public concern and counter to the fiduciary duty he accepted as a special government employee and FDA panel advisor. Such conflicts of public and personal interest jeopardize the legitimacy of one proclaiming to act on behalf of the public’s best interests.
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.
Provenge received an overwhelming vote of support from the advisory committee and recommended immediate marketing approval be granted. Those voting in the minority, 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).
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 Dr. Howard Scher’s individual services could outweigh the above demonstrated conflict of interest created by the financial interest attributable to Dr. 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.
Anonymous
The facts of this and similar cases will be exactly what a democratic administration (coming soon to the white house) will use to justify massive reforms in prescription drug development and promotion.
Lili
Provenge received an overwhelming vote of support from the advisory committee and recommended immediate marketing approval be granted. I know how important it is to cure cancer—but do you know how many advisory groups are paid off???????
My husband died becuase of the lies about all pharmaceutical medications. Americans should abide by truth, honest and ethical values. Americans do not know how to live with honest morals.
info@aksiaal.ee
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Advanced Prostate Cancer » Public Petition About Conflicts of Interest At The FDA
[...] Undisclosed Conflicts of Interest: Howard Scher, Provenge Advisory Committee Member. http://www.pharmalot.com/2007/07/dendreon-provenge-and-conflicts-of-interest/ There’s a lot more information for anybody who wants to pursue this further. If you can see [...]