Provenge, FDA Panels And Conflicts Of Interest
14 CommentsBy Ed Silverman // July 6th, 2007 // 6:01 pm
The steaming controversy over Provenge - whether the prostate-cancer vaccine should be approved; the two FDA advisory panelists who went out of their way to delay agency approval; threats made to the two docs; and outrage among cancer patients and biotech investors - isn’t going away anytime soon. In fact, it resurfaced this morning on the front page of The Washington Post.
For those following this mess, the story didn’t really add much. For those who were unaware, though, the Post provided a good round-up, complete with significance and the bitter remarks of Maha Hussain, one of the FDA panelists, who fears for her safety. Both she and the other dissenting doc, Howard Scher, required private security at a recent meeting of cancer docs, for instance.
Here’s the quickie backdrop: the FDA panel this spring voted that Dendreon’s Provenge was safe and effective. The two docs weren’t convinced, though, and wrote the agency about concerns they had with Provenge trials, triggering the FDA delay. The stock, meanwhile, was gyrating. And cancer patients and their families were outraged, prompting protests and Internet missives.
Their fury was stoked, in part, by disclosures that Scher and Hussain had conflicts of interest. Scher (pictured to the left)
has ties to other drugmakers - such as AstraZeneca and Sanofi-Aventis - with cancer meds. He’s also lead investigator for Novacea’s prostate cancer drug. And a patient group, ProvengeNow, cites info that Hussain was on Novacea’s advisory board. However, Novacea spokesman Paul Leland says the only tie to Hussain was a one-time fee she was paid for reviewing trial data two years ago.
The episode, which raises a host of thorny issues about experimental meds, could have been avoided if there were strict policies about panelist conflicts. Unfortunately, some people don’t get it. Only recently did the FDA propose barring anyone whose financial ties to industry - grants, consulting fees, stock holdings - exceed $50,000. A panel member with less than $50,000 probably couldn’t vote. But $50,000 is still a lot of money.
Congress, meanwhile, flubbed a chance to fix the problem. The House PDUFA bill limits conflicts of interest waivers to one per panel. That’s better than the Senate bill, which doesn’t limit the number of waivers. But even one is too many. Scher and Hussain may be sincere and insightful, but the perception problem gets in the way, whether FDA officials like it or not. As the Provenge debacle demonstrates, FDA panels need qualified experts - experts who aren’t vulnerable to second-guessing.
mourad zarouri
Great article. The problem with Dr. Scher is to folds. For one he didn’t disclose all the conflicts of interest he had. So the waiver was granted under false disclosures. Also, he wasn’t content with just voting no, he went further and lobbied the FDA by writing them a letter and leaking it to the press. Also, he is so corrupt that he mentioned “investors” during the panel meeting (its in the transcript). Impact on investors should not be a consideration, but it obviously shows his true colors. Novacea would have never gotten the deal they got if Provenge had been approved and Scher did all he could to make sure Provenge was not approved. HE SHOULD BE IN JAIL!!!
paul
You’re aware that Scher, immediately after the FDA turned down Provenge, failed to mention his worst conflicts of interest? Check out his interview in the Wall Street Journal:
“I try to keep to the high ground,†Scher said, adding that he doesn’t work with any companies in direct competition with Dendreon. He serves as advisor to Innovive, a small biotech not involved in prostate cancer, and works with Bristol-Myers Squibb in an unpaid capacity on early stage
drugs that may hold promise in prostate cancer. He and his wife hold small amounts of stock in Biogen Idec and Pfizer, he said.
http://blogs.wsj.com/health/2007/05/11/dendreons-ups-and-downs-at-fda-and-on-nasdaq/
Then consider his comments shortly before the Provenge advisory committee meeting:
http://www.medpagetoday.com/Urology/ASCOProstate/tb/5142
Exceprts:
” Dr. Scher said the ongoing phase III studies include trials of docetaxel in combination with bevacizumab (Avastin), DN-101 (calcitrol), atrasentan; GVAX; and VEGF-trap compounds.
He suggested that when doctors consider whether to prescribe certain treatments, “it may be time we focus less on statistical significance alone, and more on patient benefit.” He noted, for example, that just-released data from a trial of satraplatin plus prednisone did not confirm a survival benefit, but did suggest that the combination was
effective against pain, which appeared to translate into a slowing in progression of clinical symptoms.
He said, too, that many researchers are shifting focus from statistical significance alone to outcomes that are softer and more difficult to measure. ”
When Howard’s drug is concerned, he sure seems to want to loosen things up, eh? But when a rival therapy, which has the potential to set the chemotherapy establishment on its rear end, and which even he acknowledges is perfectly safe, is being considered, its time to violate protocol and write letters to the FDA to ensure its denial.
Perhaps you like I see something funny in this.
Tom Smith
Scher and Hussain needed private security at a recent meeting of cancer docs. Prostate cancer patients and their family’s need security from cancer called PROVENGE! ~5,000 men dead from PC since the decision by the FDA(known as BLACK WEDNESDAY) to delay full approval! How many more need to die before this safe and life extending vaccine is given full approval? The FDA’s own Advisory committee voted 14-0 that Provenge was safe(mild flu like symptoms lasting 2-3 days after each infusion) and 13-4 vote(yes) demonstrating efficacy! This is the first time the FDA has not gone along with a positive vote! Provenge should have received at least a “Condition Approval” Though IMHO it should have received “Full Approval”. Something smells in Denmark and in the offices of the FDA! Thank you Ed Silverman for taking a look at this most important issue to men suffering from (AIPC) and their families. I hope you take the time to dig in deeper! IMHO there is whole lot more to the story that needs to be uncovered!
Paul Haider
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.
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. Dr. Howard Scher is a scientific advisor for and has been granted an ownership interest in Proquest Investments. There are roughly 23 million shares outstanding in Novacea. According to SEC documents filed May 15, 2006, Proquest Investments (or it’s principals) own 1/3 of all the outstanding stock issued in Novacea, a company with a $220 million market capitalization. Below is a table that details ownership in Novacea by Proquest Investments (or it’s principals).
As of May 15th, 2006
Owner
Shares
Percentage
ProQuest Investments II, L.P.
1,779,767
8.0%
ProQuest Investments II Advisors Fund, L.P
75,508
0.3%
ProQuest Associates II LLC
1,855,275
8.3%
Jay Moorin
1,910,988
8.5%
Alain Schreiber
1,855,275
8.3%
Total
7,476,813
33.4%
http://secfilings.nasdaq.com/filingFrameset.asp?FileName=0000932440%2D06%2D000258%2Etxt&FilePath=%5C2006%5C05%5C24%5C&CoName=NOVACEA+INC&FormType=SC+13D&RcvdDate=5%2F24%2F2006&pdf
larry larsen
I was diagnosed with prostate cancer in July, 2004. My PSA indicates the cancer may again be rearing its ugly head. I understand from your article that there is a new therapy that was voted safe(17/17) and efficacious(13/17) by an expert advisory panel and that possibly has extended the lives of several patients by years. I also understand there is a chemotherapeutic toxin available that essentially may add a few days or weeks of life to advanced prostate cancer patients, and is guaranteed to make them wish they were dead. Evidently, the earlier a patient with recurrent cancer takes a promising new immunotherapy, the more benefit they might obtain from the therapy.
I find this all so confusing. What to do!? I assume the new therapy is or will be available soon. Certainly nobody would deny dying cancer patients the opportunity to make their own informed decision with their personal physician in a case of life or death. After all, we aren’t talking about mild diabetes or hypertension or a cold. It sounds so promising, but then it isn’t absolutey, definitely, most assuredly, 100% statistically safe.
On the other hand, a chemotoxin sounds so reassuring. I’m sure the toxin must kill the tumor cells quite dead. Yes, that’s probably 100% statistically sure. But can they give me a high enough dose to kill all the cancer cells without killing me? Oh my! Oh bother! What to do!?
Is there a wizard kind of doctor I can go to that will guide me in my decision? One that will be unbiased? One that has my life more at interest than his/her wallet? You mentioned some physicians in your article. Would they be such a physician?
Maybe I should go to a famous medical university or school or cancer center for advice. But their names seem to be so different nowadays. So do their faculty and curricula. Can you recommend one of the following that I have found. They seem to be pretty representative:
1. Hippocritic Loath School of Medicine
2. Venture Capital University School of Medicine
3. HedgeFund Medical School and Cancer Institute
4. Medical Investing and Science Advisory University
5. Big Pharma Chemotoxin Research Center
6. Making Money Speaking and Advising Medical Hospital
7. Memorial Cancer PseudoEthics Cener
8. Professional Medical Conflicts of Interest University
9. SuperSuccessful Medical Conflicts of Interest University
Thank you for any help you can give me. Patients rely on their doctors for guidance, but often the docs are busy with finance institutions or sponsoring this or that…I feel so sorry them…always on call for their brokers 24/7. Anyway, let me know which of the above facilities will have a kind, helpful wizard that will be more than an illusion behind a curtain found along the yellow brick road to Wall Street. Maybe you can do even more in-depth articles on this. Every other media has just given me a quarter and told me to call someone who cares.
Thank you so kindly
larry larsen
Kerry Donahue
Thank you for your aqrticle on Provenge. Is is a shame that a completely safe immunotheray cannot be used by terminal patients.
Many pateints (52 I think) who received Provenge are still alive and only a couple that received the placebo (from the original trials) are still alive. The immunotherapy has only been studied on the sickest of sick and may actually work even better on patients with less advanced cancer.
It is a shame that crooks like Scher are able to keep this safe immunotherapy from the patients who need it. Selection of Scher was done by Pazdur at the FDA who was trying to control the advisory committee make up. Pazdur is on one side of the inside political battle within the fda.
Ella Does Squamish :: “Provenge, FDA Panels And Conflicts Of Interest” :: July :: 2007
[...] http://www.pharmalot.com/2007/07/provenge-fda-panels-and-conflictsJuly 6th, 2007 6:01 pm By Ed Silverman The steaming controversy over Provenge - whether the [...]
Kyoto27
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.
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.
Dr. Howard Scher is a scientific advisor for and has been granted an ownership interest in Proquest Investments. There are roughly 23 million shares outstanding in Novacea. According to SEC documents filed May 15, 2006, Proquest Investments (or it’s principals) own 1/3 of all the outstanding stock issued in Novacea, a company with a $220 million market capitalization. Below is a table that details ownership in Novacea by Proquest Investments (or it’s principals).
http://secfilings.nasdaq.com/filingFrameset.asp?FileName=0000932440%2D06%2D000258%2Etxt&FilePath=%5C2006%5C05%5C24%5C&CoName=NOVACEA+INC&FormType=SC+13D&RcvdDate=5%2F24%2F2006&pdf
jason
Has anyone actually looked at the data - not some report that” I heard everyone who got Provenge is running marathons and everyone who got placebo died the next day” - I was told about Dendrion as an excellent investment before the advisory panel meeting. I looked up the data and concluded that there was no way this was going to get approved - especially given the way the new FDA acts. It does appear to be safe - but doesn’t appear to be markedly more effective than current hormonal therapy. I don’t know if this new oral has promise - I have not looked up the actual data. But I was very surprised that Dendrion was recommended by the ad board. Realize the environment we are in - If people are upset with the FDA that drugs get recalled after release. They don’t understand that EVERY med they put in their body carries some risk. So we have to decide which we want - an more open FDA that relies on physicians to make the correct choice for patients, or an FDA that avoids approving any med that might have a problem later.
I can appreciate the fact that these are cancer patients. But if you let everyone who has a “safe” med get approved do you get ahead? Safe AND effective is the way that drugs are approved now - not just safe.
jason
Larry,
Sounds like you are the perfect candidate for hormonal therapy. Avoiding chemo and giving you time for new safe and effective meds to be approved.
Lisa Van Syckel
Jason,
Safe and Effective is the way that drugs are approved now-not just safe.
Really….I take it that,that is why FDA hasnt approved the use of antidepressants for child and adolescent depression,with the exception of Prozac,and again that approval is suspicious,being,as the TADS Study by Dr John March,did not meet FDA standard for approval.
It doesnt matter how many children are harmed or killed…..
Its all about the sales,right!
Melody
So we have to decide which we want - an more open FDA that relies on physicians to make the correct choice for patients, or an FDA that avoids approving any med that might have a problem later.
I believe an FDA that relies on physicians to make the correct choice MAY be why we have the problem within the FDA that we are now witnessing. The adeverse event reporting system is so-o-o-o broken as to be a joke. The AERS was designed so patients and doctors could report adverse events; a quick or significant accumulation of data should enable the FDA to respond quickly if adverse data begins to pile up. BUT, reporting to the system is voluntary, and estimates are that only 10% of adverse events are ever reported. Patient-submitted material is anecdotal; physician reports trigger additional paperwork/data collection . . . certainly no inducement for doctors to place patient welfare first. Of late, it seems that the modus operandi within the agency is completely reactive–when the pile of dead bodies is so high it can’t be ignored–the FDA zooms into action. As a “dog person” I see an analogous situation in the canine world: a guard dog that isn’t alert enough to protect his territory nor brave enough to attack intruders will, nevertheless, bite the butt of an escaping criminal, after the evil deed has been done.
larry larsen
Jason,
Thanks, Jason, MD, right?
Very thoughtful. Have you tried hormonal therapy on yourself? I gather it is pretty much without side effects? Someone suggested I research whether there are any controversies in the literature about women taking hormones. Yes, I guess it is the doctor that should make the final decision in life and death; they have proven they don’t have any conflicts of interest. I didn’t know Provenge was an oral therapy. Jason, when you or one of yours gets the kiss of death, I’m relieved you won’t want something that has only a 1 in 40 chance of being a fluke, something that missed statistical significance by .002. I think you’re right though, those statistics wouldn’t be safe enough for you capital investment. Wise choice for you. Thanks again.
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