One month after a non-profit group accused the FDA of violating the Freedom of Information Act by failing to provide documents, the agency has forked over paperwork indicating FDA commish Andy von Eschenbach did hear from two panel members who last year urged him not to approve the Provenge prostate-cancer vaccine.
The non-profit, Care To Live, filed a lawsuit against the FDA after the agency last spring overruled one of its advisory panels, which recommended approval of the Dendreon vaccine. At the time, no one knew that two panel members took the unusual step of writing letters to Andy in hopes that he would direct the agency to delay approval. The move was allegedly orchestrated as part of a Byzantine powerplay at the agency, according to the non-profit, which also accused the two panel members of harboring undisclosed financial conflicts of interest.
The letters were written by Howard Scher, an oncologist at Memorial Sloan-Kettering Cancer who serves on the advisory board of a venture capital firm that invested in Novacea, which is developing a rival cancer med. The other was Maha Hussain, a University of Michigan oncologist. Last month, though, the FDA responded to a FOIA request by the non-profit and indicated Andy's office couldn't locate any 'responsive records' concerning the letters, despite a ‘diligent search.’
Yet, there was evidence that key letters and memos were either addressed to him directly or he was among those listed to receive copies. You can read about that right there. Now, the FDA has turned over copies of not only the letters written by Scher and Hussain to von Eschenbach, but also the e-mails they wrote him directly, which indicates the material was received by his office. (Take a look at these).
Setting aside the debate over Provenge, the belated effort to locate documents - which came only after a lawsuit and court filings accusing the FDA of violating the FOIA - doesn't speak well of the agency. There may not have been any bad behavior involved, but this is the sort of problem that members of Congress complain is a regular impediment to their efforts to better understand FDA workings. Given that HHS Secretary Mike Leavitt may face contempt charges for failing to turn over documents related to the Ketek antibiotic investigation, perhaps Andy and his staff thought twice.
21 Comments
God bless you and keep up the great work. Your blogs are extremely accurate and to the point. Thank you.
Ray Amato
Here’s yet another example where the government initially either lied or was totally inept…or both.
The evidence finally released now shows that von E received Scher’s letter via e-mail as well as direct through the U.S. Mail.
Interestingly, an e-mail from Scher to von Eschenbach, found in the same release, includes an e-mail from Steven Rosenberg (invited?) dated April 27, 2007, supporting Scher. Rosenberg is in NCI (as are Martin and Streicher, two of the people who already have been identified as being involved in the development of the Scher letter). Rosenberg, in particular, has devoted his life’s work to cancer vaccines, and it’s possible that the approval of Provenge would have impacted on his work.
Regardless, it’s interesting that as late as the end of April, a special government employee (Scher) still is lobbying the FDA commissioner to turn down the approval of Provenge. Scher could not have mounted such a campaign as a special government employee without the advice, assistance, and support of a full government employee…it’s just unheard of, in any case.
So, the question still remains: Who is the Wizard of Oz? Who's the FDA employee behind the curtain who pulled all the strings?
This whole scandal smells worse with every passing day.
The time is long past for a full investigation into the activities surrounding not only the conduct of the Provenge advisory committee meeting, but the activities of certain participants in the months that followed.
Who is Kelly Palmer at the top of the email?
And, oh by the way, Andy, I hope it's ok that I didn't include in my conflict of interest disclosure that I am the lead investigator for Novocea's Asentar, which will compete in AIPC with Provenge, and for which activity I receive substantial remuneration, and that I am a scientific advisory board member of ProQuest Investments, which owns a substantial stake in Novocea, and that I own shares of ProQuest Companion Fund, which means I have a direct financial interest in the failure of Provenge, and that Novocea and Schering Plough are currently negotiating a global development deal for Asentar that will be worth over $400 million to Novocea (but which won't happen if Provenge is approved).
These minor little things are best left for no one to know, as some might think they could cloud my judgment, and someone at the agency might question whether such conflicts could be properly approved.
And I hope it's also ok that I am by this letter departing from the established processes of the Advisory Committee. I really wouldn't want Dr. Mule and the others on the AC who actually have expertise in immunotherapy to have an opportunity to discuss fully and rebut the arguments that have been included here. I don't fully understand all this anyway, not being an immunologist, but those who were asked by Dick to help write this letter must know what they are talking about.
Finally, Andy, it's okay that this letter get leaked to the Goldberg's at the Cancer Letter if to do so will build a little more cover for you. I know you have a minor revolt on your hands over who gets to evaluate cancer drugs at the agency, and maybe this will give you what you need to delay approval and thus help quell the threats of a demonstration over that turf battle and that would be so embarassing at this critical time for you over on the Hill.
Yours truly,
Howard
Lucy, in response to your question regarding Kelly Palmer: I believe he/she works in Von Eschenbach's office. His/her name appears in another FOIA suit involving the FDA at this URL: http://www.judicialwatch.org/archive/2007/FDA.Opp2Motion.pdf
This is not the first time the FDA is on the front burner for disregarding FOIA requests!
My guess is that he/she is an administrative assistant or secretary, but I'm not sure.
Thanks to Ed for staying on top of this stink-heap of a story!
It makes me wonder just who does the FDA and Von Eschenbach think that they work for.
Answer. For themselves.
There has been so much dirty laundry here Ed you should open up a dry-cleaning service....
Ray
Just so no one reading this latest chapter in the on-going saga of the FDA and Dendreon's Provenge for the treatment of TERMINAL prostate cancer victims, let me put out 3 items:
A. Dr. Howard Isadore Scher of Memorial Sloan Kettering in NYC was granted a Conflict of Interests waiver by the FDA based upon his certifying to the FDA that he had 3 COI.... 1 stock holding and 2 competing company conflicts.
B. Internet research suggests Scher has at least 17 Conflicts of Interest; this data suggests that Scher was less than honest in his application for a Waiver to the FDA.
[BTW, once the #hi@ hits the fan, this apparent omission on Scher's part can provide the FDA with "plausible deniability" which could then put Scher out there flapping in the breeze all alone legally, imo.]
C. Those 17 Conflicts of Interest for Dr. Howard Isadore Scher found on the internet are:
[NOTE particularly items #1 and #17]
1. NOVACEA: grants & research support; STUDY CHAIR of DN-101;
.... and 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 MYERSSQUIBB: consultant, grants & research
6. MILLENNIUM PHARMCEUTICALS: grant of research support
7. COUGAR BIOTECHNOLOGY: principal investigator; advisoryboard;
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 PCClinical Trials-P1 and P2
15. AMBRILIABIOPHARMA INC: Principal Investigator PCK3145, Phase I/II
16. MEDIVATION, INC: principal investigator MDV3100
17. PROQUEST INVESTMENTS, Board of Directors, Advisor. Invested in Novacea.
Our Government seems hopelessly helpless. Obvious corruption, obvious CORRUPTION, OBVIOUS CORRUPTION! No matter how loud you scream it, nobody investigates....not Republicans, not Democrats. The undisclosed COIs of Scher are glaringly apparent, but we shouldn't forget these other nuggets of ugliness.... 1. The FDA posed the efficacy question improperly at the Provenge FDA Advisory Committee. If not for an AC panelist's request that the proper question be asked, the FDA would have derailed Provenge's approval then and there. 2. Padzur passed notes to Scher at the AC's break....is this normal? 3. The FDA asked for more data in the Complete Response Letter? Advisory Committees are assembled once the FDA decides enough data has been collected. 4. The AC voted 17-0 on the safety of Provenge and 13-4 on the efficacy of Provenge. For the first time in history, the FDA went against the AC's approval recommendation in the case of a life threatening illness with no other safe alternate treatment. 5. Today, approximately 80 Americans will die from the ravages of prostate cancer. Nope, nothing wrong here.
Unless this travesty is reversed and FDA approves the use of Provenge ASAP, I fear my brother will soon be one of the 80 Americans who will wrongfully die each day from the ravages of PC thanks to the conflicts of interest and greed of Scher and Hussain. I hope there is a special place in hell for these unscrupulous docs.
Pros and Cons to make you think: Just because they sent emails, doesn't mean he read it. He gets hundreds of emails a day and probably has his secretary screen it.
Just because the advisory committees members are active in the science with a competitor, doesn't mean they think that their own company is great. Hard to believe, but many of these advisors are there to tell companies how they need to improve. In fact some studies show those guys vote against their own companies more than they vote for it. They are the canaries in the coal mine. Some. Not all.
Provenge is very promising, but it's hard to make. Manufacturing biologics is hard. It's not profitable generally. There are often dangerous variations batch to batch, and researchers are notorious for not following directions. After all, that’s how researchers make great discoveries. But it really f*s up manufacturing when they have to follow the recipe. Provenge is very very difficult to produce. Like many biologics, it may be unapprovable because the studies are unreliable because each batch was wildly different and the data with patients from different batches can't match up. Just because you have cancer doesn't mean companies are entitled to sell you something they don't know how to make.
The NCI contacts, where A-VON came from, probably mean more to him than the business contacts.
Let's bring back Dr. David Kessler. Hillary? Obama? Do you promise?
exFDA, I found your post interesting, initially, but every time I read it, it strikes me as simply nothing more than another effort to 'debunk' Provenge.
Too many seemingly excessive, almost 'absolute' claims which purport to make your point. But no evidence, nor supporting arguments. Just ... well ... rhetorically inflated claims.
An invitation: please come to the Investor Village/DNDN board (home away from home for many of us who cherish Ed's humor and intelligence laden 'abode'). There you/we could have an extended discussion with several M.D's., some biologists, a few professional mathematicians and statisticians and other members of the general public.
If you are correct I think, after the initial shock, protests etc., you would find most everyone grateful for the enlightenment. If you are not correct, well ...?
exFDA is concerned that"Provenge is very promising, but it’s hard to make." The only concern about manufacturing Provenge is the concern by competitors who know very well that Dendreon can use its large-scale autogolous vaccine processing capabilities, its antigen cassette technology and basic BLA filing, with a sBLA, to bring many new cancer vaccines, each with a high therapeutic index, faster and cheaper to patients, than the time and cost that it would take to bring one monoclonal antibody or small molecule drug to patients.
The ease of Dendreon's commercial scale manufacturing is just one more reason why Dendreon is unique in the so-called biologics space. I suggest exFDA talk to Dendreon's Dr Urdal.
exFDA, What do you know about Dendreon's Provenge manufacturing process to suggest it can't be produced consistently and reliably?
Is this just more bunk!?! What does manufacturing Provenge have to do with proof that Dr. Scher lobbied his personal friend, Commissioner von Eschenbach, well after the Advisory Committee to delay Provenge whereby Dr. Scher did gain financially from the decision.
Dr. Francesco M Marincola, who himself participated in the Provenge AC, stated that his role as member of the Advisory Board was "to express his opinion during the meeting but it would be ill advised to influence the FDA decision beyond that point."
As employees of the FDA, they each have a fiduciary duty to up hold to all Americans. The foundation of their position is based upon good faith, loyalty, and trust. Do you honestly consider that the FDA has responded to the FOIA requests in good faith? The FDA to this day has not provided any documents from Dr. Pazdur who, it is widely suspected, leaked confidential letters to a periodical called "The Cancer Letter" that was inimical to the approval of Provenge.
As a fiduciary, each must not put themselves in a position where their interest and duty conflict. In the case of Howard Scher, his fiduciary duty at the FDA interfered with his fiduciary duty at Proquest Investments. This is like a lawyer representing both the plaintiff and the defendant in the same legal matter. The lawyer cannot make the either the plaintiff or the defendant’s interests a top priority if both the plaintiff and the defendant’s interests are diametrically opposed.
Knowing of Dr. von Eschenbach’s own personal history of conflicts of interest, how is the public to believe that Dr. von Eschenbach is serious about enforcing FDA policy regarding disclosure of conflicts of interest for Special Government Employees participating in FDA Advisory Committees? I believe the Commissioner himself was instrumental in the Provenge decision. Such conflicts of public and personal interest jeopardize the legitimacy of one proclaiming to act on behalf of the public’s best interests or under the auspices of science. The FDA subjected the terminally ill AIPC patients to more suffering whereby a few would benefit financially.
It is clear to me that the science and normal process at the FDA was overturned by a small group of people with inordinate influence and subverted the process and had nothing to do with producing Provenge consistently and reliably. The Provenge advisory panel confirmed that Provenge met all the criteria for marketing approval. 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.
exFDA's veracity as an ex-FDA employee is highly dubious. That handle is likely self-given in order to grant said self some respect/authority. However, the laughable content in that post either shows complete ignorance or complete dishonesty: "...Provenge is very promising, but it’s hard to make. Manufacturing biologics is hard. It’s not profitable generally. There are often dangerous variations batch to batch, and researchers are notorious for not following directions. After all, that’s how researchers make great discoveries. But it really f*s up manufacturing when they have to follow the recipe. Provenge is very very difficult to produce. Like many biologics, it may be unapprovable because the studies are unreliable because each batch was wildly different and the data with patients from different batches can’t match up."
You doofus, of course the batches are going to be 'wildly different,' and of course 'the data with patients from different batches can’t match up.' Provenge is an autologous vaccine. Do you know what that means without using google or wikipedia? OK, I'll help. It's patient-specific. The patient gets his blood drawn, and the dendritic cells are removed and sent to the mfg plant, where they are combined with a prostate cancer-specific antigen and an already improved immune system booster to form Provenge. No two sets of blood from different patients are going to be alike. Did you think Provenge is like GVAX? If you really did work for the FDA, were you fired for incompetence?
For a scientific blog, there's a lot of Ad Hominem attacks here. Pass chemistry, flunk logic? Flunk both?
Even autologous vaccines have to have identifiable similarities for a clinical study to produce good data. The purpose of a clinical study is to show how a product works across an entire patient population. If it doesn't show that, the "study" has an N of one. If the product is that unique, then they can't sell it as a commercial drug. Commercial drugs and biologics are required by law and regulation to have uniformity from batch to batch. If it doesn't, maybe it can be sold as an indivdualized treatment, one patient at a time, but not as a drug or biologic. My guess is insurance wouldn't pay for it under those circumstances, or if they would, it still wouldn't be commercially viable. So like every company, they need to show with substantial evidence from clinical trials that they can make a product with the same critical characteristics every time.
Blood can be an autologous product, and it's regulated the same way. It can have variations, but the critical characteristics have to be identified, tested for and present, or else it's not blood, and is adulterated and misbranded. Dendreon must be held to the same standard.
I'm not saying it's not frustrating, and a treatment can be dismissed. I'm saying like every product, it must prove itself. The burden is on Dendreon. And many R&D and biological companies won't follow a protocol or manufacturing step to save the company, themselves, or their patients.
These issues won't necessarily be dispositive of the product. A-Von might not have seen the emails. The advisory committee membership issue is also troubling, but we've heard that for decades, too. The alternative seems to be to pay the experts enough to give up the other jobs (and taxpayers have been unwilling to fully fund FDA for 20 years or more) or hire people whose expertise is so low or unappreciated that no one else will pay them for it. I'm troubled by all the allegations raised here, but even if it's all true it doesn't prove that any particular product deserves approval.
exfda... "Provenge is very promising, but it’s hard to make. Manufacturing biologics is hard. It’s not profitable generally. There are often dangerous variations batch to batch, and researchers are notorious for not following directions."
Complete rubbish. "Manufacturing biologics is hard"... huh? no, not hardly. Developing biologics...sure, but not manufacturing.
"dangerous variations batch to batch".. Really now? please do tell.
The best way to tell that I'm ex-FDA is I think it's hilarious that anyone would claim to be ex-FDA "in order to grant said self some respect/authority." Like the respect/authority FDA gets in these comments? Like the respect/authority FDA staff gets from this administration? Like the respect/authority of saying FDA is full of criminal masterminds who collaborate with industry in an efficient and secret conspiracy? Or like the respect/authority of saying FDA is a bunch of buffoons who can't evaluate clinical trials or drug manufacturing? Which one is it? Brilliant or incompetent? If you think manufacturing is easy, not only have you never done it, but you've never bothered to read the warning letters and recalls in plain view on FDA website. Some companies clearly can't even mix proper amounts of vinegar and baking soda together to make an elementary school science project, much less grow cells in an aseptic environment using proper procedures, sterilized equipment, trained staff, and proper documentation of their manufacturing, cleaning and equipment. I'm not saying Dendreon had any of these problems. I'm not privy to that, and if I did know I couldn't say. I'm not saying Von E. and all the advisory committee members acted properly, either. I don't know, but it looks bad. I'm saying that Everyone involved could be a crook, but that doesn't mean Dendreon has an approvable product that they can make repeatedly. And obviously people wish it could do so, or they'd stop and think instead of name calling.
By the way, if you want the product, and if Dendreon can make it, you can probably get it whether it's approved or not. FDA will help your doctor file a Treatment IND and you can contact the Office of Special Health Issues at http://www.fda.gov/oashi/home.html. But if the reason you can't get it is the manufacturer can't make it, they won't be able to reveal that is the reason, because that's confidential commercial information.
To Ex FDA - Stick around, we really need your insight here!
Welcome!111
exFDA, "...it doesn’t prove that any particular product deserves approval."
That's not what the overwhelming majority of Advisory Committe members voted in the case of Provenge. The decision denying Provenge immediate marketing approval was made in a vacuum by individuals who have benefited from promoting a competing product to Dendreon.
Excellent point. Let's focus on the evidence that convinced the majority of the committee.
FWIW, I think any political appointee and his entourage these days are just shills for the administration and unconcerned about scientific evidence. I don't trust those guys, either. Remember the Surgeon General, Dr. Carmona, who said he was "surprised" he was asked to ignore science and spout the party line?