A Bitter Irony In The Provenge Saga
21 CommentsBy Ed Silverman // April 9th, 2008 // 4:47 pm
At the heart of the controversy over the Provenge prostate-cancer vaccine, which an FDA panel last year recommended before the agency delayed approval, are allegations of undisclosed conflicts of interest involving two of those panel members. They quietly wrote FDA officials to urge a go-slow approach and their actions have since drawn derision and fury from prostate-cancer patients and investors in Dendreon, which is developing Provenge (back story).
One of those panelists was Howard Scher, a prominent oncologist from Sloan-Kettering Memorial Cancer Center, who also sits on the scientific advisory board of ProQuest Investments, a venture capital firm that held shares in Novacea, a small company developing a rival prostate cancer med. Around the time of the FDA decision, Novacea signed a development and marketing deal with Schering-Plough that was potentially valued at more than $450 million.
Well, today, that deal crashed and burned because a clinical trial found an unacceptable number of deaths associated with the Novacea med. In a statement, Novacea ceo John Walker reiterated earlier remarks about seeking “strategic options.” Novacea shares fell nearly 4 percent today to close at $2.61. Last May, however, the stock hit $17.25.
Scher has studiously avoided responding to the Provenge controversy, but comments made today on InvestorVillage take him to task. Meanwhile, prostate cancer patients are continuing their ad campaign to persuade FDA officials to approve the vaccine. Their argument - Provenge may save lives. To that refrain, they’re now adding the ironic news that the Novacea drug had the opposite effect.
Phil Martin
Boy, Howard’s investment in Novacea must be just about worthless by now.
Maybe he can shake down some other outfit and then go after its competitors with an FDA non-approval for a perfectly safe and efficacious drug, like Provenge.
Compared to him, the creeps who are abusing their government credit cards for $13,000 lobster dinners look almost saintly.
At least they’re just stealing and not actually contributing to the early death of anyone.
Poop Doggy
Ed, PLEASE! To quote your report:
“They quietly wrote FDA officials to urge a go-slow approach and their actions have since drawn derision and fury from prostate-cancer patients and investors in Dendreon, which is developing Provenge.”
The only thing quiet was the secrecy under which at least one of the letters was written. Thereafter, there was NOTHING quiet about the way the contents were distributed. One needs only to look at how quickly the Goldbergs of the Cancer Letter got their mitts on the letters and had them in the public domain.
The questions remain: Who REALLY wrote the letters? Who REALLY leaked the letters and for what purpose? And why does Scher believe comments critical of his actions must be removed from another web site for which he is an adviser?
Please don’t misunderstand, Ed. I applaud your ongoing efforts to keep this story alive. But to call the letter-writing campaing quiet is a misnomer in my judgement.
Thanks!
AMMASS
The FDA has no shame
Ed Silverman
Dear Poop,
Quiet as in ‘behind the scenes,’ or ‘not out in the open.’ And I’ve added a link - click on ‘back story’ - to give readers more insight into the allegations that have been swirling around.
Regards
ed
anonymous
you are spending more time on the provenge story than it deserves. sounds like you are a burned dndn investor yourself. get over it. all these conspiracy theories are a waste of time and a degenerate form of journalism.. oh, wait, it’s not lower than reporting on a child-pornography indictment of a pharma exec.. who in the world cares to read shit like that in a blog about the business of healthcare?.. has the tabloid culture complete warped our minds?? is news-worthy equivalent to scandalous? I for one, do not give a shit about child-molesting pfizer execs or disgruntled investors of a mismanaged cancer start-up. Surely, there are more important topics out there…
Bruce
Hi Anonymous,
I think that Ed has done a great service to his readers by bringing this story into the open. In fact, I don’t remember reading anywhere else. And since he is an excellent reporter, he will stick with the story until it comes to its natural end. For the many men with prostate cancer waiting for something, I hope that “something” comes sooner than later.
Bull
The most important remnant of the Asentar saga as it realtes to Provenge and the approval of effective AIPC treatments is simply “why”.
“Why” hasn’t Congress, HHS, or the FBI investigated Howard Scher for his numerous undisclosed conflicts of interest?
“Why” has he not been prosecuted for violating the AC Panel bluse sky provisions in the letter writing campaign to the FDA (leaked to The Cancer Letter)?
It would appear he has been given a “get out of jail free card” for his crimes.
Ed Silverman
Dear Anonymous,
The reason I have followed the Provenge controversy is very simple - it speaks to the ongoing debate over approval of experimental meds and the way the FDA handles conflicts of interest, alleged or otherwise.
As to the Pfizer patent counsel, he holds a high-ranking position at a major drugmaker. He allegedly violated a law, yet he is in a position of influence when it comes to ensuring Pfizer follows the law and pursues its rights. We care about the doings of high-ranking managers at drugmakers and we write about patents a great deal.
And there are, roughly, 10 or so posts every day on Pharmalot about all manner of topics - preemption, compulsory licensing, DTC advertising, job layoffs, patent reform, pricing, safety, FDA reform and oversight. The list goes on. It’s a big, busy pharma world and there’s room for a great many topics.
Moreover, importance is in the eye of the beholder. I have a great many readers/viewers whose work and interests encompass different backgrounds and mindsets. What’s of interest and importance to one may not be to another. I have to consider all of them, though, as best I can when I choose to ignore certain topics.
Thanks for stopping by,
ed
Poop Doggy
This is the Poop thanking Ed! That certainly adds the necessary color.
Matt
Everyone knows that conflicts of interest at the FDA can only be permitted as long as they are in favor of drug approval.
MD doc
No Matt,
the point is people are dying because inept/corrupted physicians are regulating drugs that get approved that shouldn’t or drugs that get delayed/rejected that should be approved, at least conditionally. I use “physicians” loosely as they are obviously conflicted and justify themselves by hiding behind statistics. That’s not medicine; evidence based or otherwise.
Gates
Maybe Scher will have to face a judge here before he faces the final Judge. We can only hope and pray he does! Up to 30,000 men have died so far as result of his greed and corruption.
MyPharmalotID
The paramount questions that only an investigation can answer are:
• What were Dr. Scher’s concerns relative to Provenge becoming the new “standard of care” (if it were to have been approved) in terms of his not being able to fully enroll patients in the ongoing Asentar Phase 3 studies as well as in other chemotherapeutic trials (e.g., involving Taxotere) in which he was engaged at the time? How did this affect his behavior at, and following, the AC meeting?
• Who asked Dr. Scher to write his infamous letter to the FDA disparaging Provenge shortly after the favorable March 29, 2007, AC meeting?
• Who helped Dr. Scher write his letter to the FDA? At least one draft of Dr. Scher’s letter (v.3) was found on a PC in NCI, and at least one NCI employee attended a meeting called at the FDA to discuss this letter. (Letter and Information Source: NCI FOIA request and telcon with the NCI FOIA officer)
• Who leaked the letter disparaging Provenge written by Dr. Scher (as well as those letters written by Drs. Hussain and Fleming) to The Cancer Letter? (Letter Source: FDA FOIA requests)
• At the time of the Provenge AC meeting, Dr. Scher was the co-lead on Novacea’s Phase III Asentar drug trials for prostate cancer…a drug that was being developed in direct competition with Provenge. What impact did this have on Dr. Scher’s judgment and activities during and in the months following the AC?
• Dr. Scher is on the Scientific Advisory Board of ProQuest Investments, a healthcare venture capital firm. Internet sources also show him to be an officer and a member of the board of directors of the same firm. At the time of the Provenge AC meeting, ProQuest Investments owned in excess of 8% of Novacea. What impact did this have had on Dr. Scher’s judgment and activities during and in the months following the AC?
• Just 3 weeks after the FDA sent Dendreon a Complete Response (“Approvable”) letter, Novacea signed a $440 million co-development deal for its late stage prostate cancer drug, Asentar, licensing product rights to Schering-Plough Corporation. Deals such as this can take up to a year or more to develop and mature. What did Dr. Scher know, on March 29, 2007, regarding the soon-to-be-announced Novacea/Schering-Plough agreement on Asentar? (As we know, that deal was cancelled today.)
• What would have been the general nature of the financial impact on ProQuest Investments and Novacea as a result of Provenge being approved in May, 2007? It can be concluded, certainly, that the Asentar trials (and, thus, Novacea’s stock price) would have suffered and that the deal with Schering-Plough would not have been concluded on such generous terms, had it been concluded at all.
Calls for an investigation into this matter have come from many quarters, not the least of which was one in December 2007 from Congressmen Michael Michaud, Dan Burton, and Tim Ryan (at 11). On February 13, 2008, however, Congressman Dingell’s House Committee on Energy and Commerce responded to the call for hearings in the matter of conflicts of interest (COIs) regarding how the FDA handled Dendreon’s application for Provenge by rejecting the request on the basis of two arguments:
• “FDA has not yet made a final decision on this product, and it is the practice of this Committee to allow a regulatory agency such as FDA to complete its statutorily-mandated processes and render a final decision before initiating formal investigative action.”
• “A preliminary investigation into the record of the March 29, 2007, Open Session of the Cellular, tissue and Gene Therapies Advisory Committee that reviewed Provenge shows that the two advisory panel members you mentioned in your letter [Dr. Howard Scher and Dr. Maha Hussain] were granted waivers in compliance with the conflict of interest rules in force at that time.”…”Importantly, since the advisory panel that considered Provenge met, a new law strengthening conflict of interest provisions now governs FDA advisory panels.”
Unfortunately, neither statement has anything to do with the original request for hearings!
In their original letter of December 13, 2007, to Mr. Dingell, et al., Hon. Michael Michaud, Dan Burton, and Tim Ryan noted that:
“Prostate cancer activists have raised questions about two of the negative voters [at the March 29, 2007, Provenge AC meeting], academic medical oncologists Maha Hussain and Howard Scher. Dr. Howard Scher is lead investigator for a competing cancer drug made by Novacea and is listed as an adviser to a large venture capital firm that is also a major investor in Novacea. We believe the FDA should not be appointing scientists leading the testing of a rival drug for another firm onto the advisory committee evaluating Provenge nor should the FDA appoint an adviser to a large investor in such a competitive firm as a panel member. It is important that Congress examines possible ethical violations of these panel Members considering the viability of potentially important life-saving drugs.”
Simply put, the three congressmen (and other congressmen who supported them, including Congressman Patrick Murphy of Pennsylvania) were asking the Committee to investigate the COIs of Drs. Scher and Hussain. They were not asking the Committee to force the FDA to approve Provenge; protocols already are in place to address that issue later this year or in 2009.
As to the waivers granted, citing the fact that a new law strengthens COI provisions basically closes the door after the horse has left the barn. The fact is, had the FDA acted in good faith prior to the Provenge AC meeting, it would have rejected Drs. Scher’s and Hussain’s waiver requests. A study published by BioCentury, The Bernstein Report On BioBusiness®, March 26, 2007, noted the following:
“Under the draft guidance, Scher either would be prevented from voting or excluded from the meeting.”
As regards to Dr. Maha Hussain:
“The waiver notes that Hussain is the principal investigator on a research contract awarded by a competing company for a product that is not related to Provenge. Under the draft guidance this probably would not be considered a conflict. However, the fact that her husband owns stock in three competing companies, valued at $15,000-$300,000, would at minimum prevent her from voting. If the total value of the stock exceeds $50,000, Hussain wouldn’t even be at the table if the new policy were in effect.”
Vince Tolino, Director, Ethics and Integrity Staff, FDA, should never have forwarded Scher’s and Hussain’s waiver requests to Randall Lutter, Ph.D., Associate Commissioner for Policy and Planning, FDA, and the latter never should have approved them.
Since May 8, 2007 (the date that Dendreon, the maker of Provenge, received its Complete Response letter from the FDA, requesting additional data that could take 1 to 2 years to acquire), more than 27,000 men have died of prostate cancer (PCa), many of whom could have been helped by Provenge.
Kerry Donahue, Esq.
When the Scher and Hussain letters were leaked to the press by the writers, or by the FDA, or by the three conspiring together, the press only reported the body of the letter.
At the time of their release we did not know that they were sent and received by Pazdur, Woodcock, Goodman and von Eschenbach. We also did not know that they were written on Memorial Sloan Kettering and University of Michigan letterhead. We also did not know that NCI employees helped with the letter campaign. Through FOIA responses we now know that the lobbying by these two doctors absolutely 100% happened.
We still do not have the e-mails that accompanied transmittal of the letters to Richard Pazdur because he refuses to provide them as requested by CareToLive in August 2007, per their Freedom of Information Act request. Dr. Pazdur claims he needs more time to be able to locate them and make a copy of them for us.
That those Doctors, for reasons other than the science, sabotaged Provenge, is a disgrace not only to their role as special governemnt employees, but a disgrace to their respective institutions.
Now, after the FDA has been made fully aware of the lack of due process given Provenge, they continue to do nothing to rectify the mistake. They refuse to put the due process back in. The lack of action on behalf of the FDA, now knowing what occurred is a disgrace that all Americans should be furious over.
The FDA by federal law must properly respond to a Citizen’s Petition, a law they have thus far refused to comply with in this matter.
Craig
Thanks Ed for following this story. The whole sordid affair is such an indictment of not only FDA Commissioner Andrew von Eschenbach and the corrupt characters such as Dr. Scher, but also of our whole government…staring with President Bush and HHS.
It is almost unbelievable that while roughly 30,000 men in America die from PCa each year, a vastly safer and superior treatment sits idled for potentially years.
Why hasn’t this story been picked up by a hundred reporters/editors/producers such as yourself across America? Where is the outrage?
The degree of indifference demonstrated by the vast majority of those whose positions grant them the ability to rectify/expose/investigate this travesty is astounding.
The legacy of innocent blood, needless suffering, and stolen hope will stain the reputations and dog the consciences of all those who engineered the denial of Provenge and of those who failed to rectify the injustice.
delta doc
This is more about the graft, corruption and absolute autocracy in which the FDA operates little differently than as in a dictatorship.
Civil disobedience is the only means this corrupt system will be changed. It worked for AIDS and works for breast cancer patients.
Why can’t it work for everyone else?
suzy_q
You have to wonder if this is the beginning of the end of Dr. Scher’s little gravy train.
William McGrath
I’m 83. I’ve served this country in two wars. I’m beginning to regret it.
Tony F
Why on Earth would a previously well-reknown cancer researcher and physician prostitute himself as Scher appears to have done with the only apparent reward being money… more and more and more money?
For those unaware of the specifics of Dr. Howard Isadore Scher’s alleged Conflicts of Interests, here’s the details.
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 and please particularly note #1 and #17:
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. CONFOMA THERAPEUTICS: scientific advisory board
14. DEPARTMENT of DEFENSE: Principal Investigator PC Clinical Trials-P1 and P2
15. AMBRILIA BIOPHARMA INC: Principal Investigator PCK3145, Phase I/II
16. MEDIVATION, INC: principal investigator MDV3100
17. PROQUEST INVESTMENTS: consultant, scientific advisory board; Limited Partner FINANCIAL interest
There appears to be a significant and disturbing difference between his 3 disclosures to the FDA and the alleged 17 COI’s found so far on the internet.
Even more disturbing is the FDA’s Office of Inspector General and others investigators at the FDA and HHS to whom this information has been supplied and their apparent failure to investigate these charges over the past 10 months.
Yet, last week when several floral bouquets were sent to Dr. von Eschenbach, FDA Commissioner, they sprang into instant action within 1 business day to “investigate” who sent the flowers.
Why did Alison Martin at NIH help Scher with his post-AC letter urging non-approval of Provenge? (per FOIA documents)
One may draw the parallel that allegedly the FDA’s Richard Pazdur is the moral equivalent of Spitzer’s East Side NYC’s madam, Kristin Davis with Pazdur having Scher and Hussain in his stable and doing his bidding.
With approximately 83 men dying daily of AIPC, the total deaths since May 9, 2007 are 27,805.
Approvenge Provenge (at least conditionally) so that prostate cancer patients and their physicians can decide whether or not these TERMINAL cancer patients should have it or not.
Scott
An even greater irony occurred earlier this week when, just over one year after an FDA Advisory Committee of experts recommended approval of Provenge, another cancer vaccine, developed by an American company, was granted marketing approval in Russia, though it had not been approved in the U.S.
Apparently Russian patients, in consultation with their doctors, will be able to decide whether to try that drug for the indicated condition, whereas in the USA, patients, in consultation with their doctors, have no option to decide whether to take Provenge, which an independent panel of experts found both safe and efficacious for AIPC based on years of clinical trials and which even scientists (Schlom, et al) at our National Cancer Institute wrote in a peer reviewed journal is effective in affording a survival benefit.
At least on that issue, which country’s citizens have greater freedom, Americans or Russians? Sad. Sad not just for the hundreds of thousands of American prostate cancer patients, sad for our democracy, or should I say, autocracy. The Provenge story is a prime example of how we are no longer a democratic republic of, by and for the people. I love my country, but I have a very heavy heart.
paul_1149
Ed, this story deserves all the coverage it gets, and I trust, happily, that your clickometer supports that thesis as you continue your great job.
Cool that I just discovered your affiliation with the Star-Ledger. That paper has a great rep for covering pharma. I’m not too far from you, in southern NY.
All the best,
paul