Provenge Activists Pressing Their Fight, Again
14 CommentsBy Ed Silverman // August 4th, 2008 // 9:25 am
What are the odds the FDA will reverse its controversial decision last year to delay approval of the Provenge prostate cancer vaccine? They would appear to be low, but a diligent group of patients and investors last week continued a two-pronged attack that is, so far, yielding mixed results.
In one development, their lawyer argued before the US Court of Appeals for the Sixth Circuit in Cincinnati that judicial review was required because of a lack of transparency and accountability in the way the FDA decided to delay approval for the Dendreon vaccine after a recommendation by an FDA panel. The activists charge this came amid undisclosed conflicts of interest by two FDA advisory committee members, who quietly wrote FDA offiicals urging a go-slow approach, and Byzantine agency politics involving the head of the oncology drugs office.
“The fact is that the FDA has never stated an official reason why they denied approval to the Provenge (application). We do not know exactly how the decision was made, who made it, how it was made, whether there was a committee, was there a meeting, who attended the meeting or what parameters were the basis of the decision,” Kerry Donahue, their lawyer, writes us. (Back story).
Meanwhile, the National Cancer Institute released long-sought documents the activists hoped would help prove their case that officials from the FDA and the NCI conspired to draft the aforementioned secret letter to FDA officials. However, the documents - largely, a string of e-mails - are inconclusive and, not surprisingly, contain redacted portions.
The battle has been largely ignored by the mainstream press and a Congressional committee declined to investigate, partly because the FDA has the right to request more data before issuing approvals and some believe the fight is really driven by angry Dendreon investors. However, the Provenge affair has also figured into the national debate over whether experimental meds should be made available to the fatally ill and raised questions about the FDA’s handling of conflicts of interest. So stay tuned.
Paul
Recs: 29 Re: NCI FOIAed documents just posted on the CTL Web site…
I sure would like to see the redacted reply to Alison Martin when she told Howard Scher that the NCI was abuzz about the Advisory Meeting decision and then asked for Howard to comment as to whether he was conviced. His entire reply was redacted “Personal Information Withheld”. Hmmm.
Then in the following reply to Dr. Scher, Alison Martin responds “Glad to hear letter being drafted.” (Doesn’t sound as if the preceeding message from Dr. Scher was very personal in nature. Rather, it spoke of writing letters and Provenge approval. Then Alison Martin proceded to discredit CBER as less clinically savy.
Ed Silverman
Hi Paul and others,
I’ve also posted a link to the documents released by the NCI in this post. Just click on ‘the documents’ in the fourth graph where the e-mails are mentioned.
Regards
ed
MyPharmalotID
The NCI Stretch (As in “stretch of the imagination”)
From the recently released FOIA information:
Alison Martin at 9:49 pm on March 30th, indicates that she could not attend the AC, but that it’s the buzz at NCI. She – and others at NCI – are apparently confused as to what had transpired and are not sure whether or not Provenge would be approved.
At this point, there is a break in the time record and the start of a new thread by Scher (March 31; 8:49 am, a Saturday); the contents are deleted in their entirely. The claim is made that the message contains personal information and so, the information is withheld.
The response from Martin, at 16:15 (4:15 pm) the same day puts this assertion by the NCI FOIA office to lie. To wit: Martin says: Glad to hear letter is being drafted. If that division’s [CBER’s, no doubt (Cohen)] vote suggests it be considered for approval, I was wondering if it then could go to ODAC [headed by Dr. Maha Hussain (Cohen)] , which is more clinically savy (sic), i.e., this is just a step in a process.
Thus, the earlier statements by Scher that were redacted in their entirety by the NCI FOIA office did contain material that was germane and relevant to the CTL FOIA request, and they should not have been withheld. Further, Scher, in the earlier e-mail, told Martin that a letter was being prepared, though it’s not possible to glean, from Martin’s response, whether Scher confided in Martin that he had been asked to write a letter (as some people believe) or simply that he an others were preparing a letter. (Recall that version 3 (v3) of the so-called “Scher letter” was found on Alison Martin’s computer at NCI in early April, 2007, indicating that she, among others at NCI (e.g., Streicher, who attended a meeting at the FDA regarding the letter) were assisting Scher in the preparation of “his” letter. Note, too, the disparaging comment made by Martin regarding the capabilities of “that division” (i.e., CBER) vs. ODAC. It’s no secret that neither CDER nor NCI have much regard for CBER and, in fact, have undermined the latter at every opportunity.)
So, what we have here, my friends, is the equivalent (from our vantage point) to the 18½ minute gap in the Nixon tapes…a gap in the record that contains significant, relevant information that most certainly is NOT of a personal nature. But it is being withheld from view, to be sure, with as much certainty as whatever was on the tape that Rose Mary Woods erased on October 1, 1973 while transcribing material recorded by President Nixon.
Here’s a toast to “the NCI Stretch”…only this time, it takes a real stretch of our imagination to believe that what is being withheld really is personal information.
Rather, it appears to be something so sensitive as to be a real embarrassment to NCI, the FDA, and the U.S. government in general! It is highly possible, in fact, given Dr. Martin’s response to Dr. Scher’s e-mail, that the material being withheld really is most incriminating and lays bare the essence of the conspiracy to sink the approval of Provenge.
18½ minute gap tape
http://en.wikipedia.org/wiki/Watergate_tapes
Nixon appointed another special counsel, Leon Jaworski. The White House then agreed to comply with the subpoena and gave some of the subpoenaed conversations to Chief Judge Sirica. The White House informed the Court that two subpoenaed conversations had not been recorded, and that an 18½ minute gap existed on a third tape.
Rose Mary Woods demonstrating how she may have erased tape recordings (see wikipedia Web site for picture)
On November 8, 1973, Nixon’s secretary, Rose Mary Woods, testified
The buttons said on and off, forward and backward. I caught on to that fairly fast. I don’t think I’m so stupid as to erase what’s on a tape.
Later that month, she testified she had made “a terrible mistake” during transcription. On October 1, 1973 while playing the tape on the Uher 5000, she answered a phone call. Reaching for the Uher 5000 stop button, she testified that she mistakenly hit the button next to it — the record button. For the duration of the phone call, about five minutes, she kept her foot on the device’s pedal, causing a five-minute portion of the tape to be re-recorded. She insisted she was not responsible for the remaining 13 minutes of buzz.
Woods was asked to replicate the position she took to cause that accident: seated at a desk, reaching far back over her left shoulder for a telephone as her foot applies constant pressure to the pedal controlling the transcription machine. Her extremely awkward posture during the demonstration — dubbed the “Rose Mary Stretch” — resulted in many political commentators questioning the validity of the explanation.
Dan
The Unavailability of Provenge and the Disappointment of Those With Deadly Prostate Cancer
*FDA’s mission statement: To promote and protect public health
Terminal patients are those who are not expected to live due to usually illness such as advanced prostate cancer (cT3). If the patient has 6 months or less to live, those patients are considered terminally ill. Regardless, if a patient is terminal, they are without a cure or tolerable treatment for their illness presently. Since such patients will likely die in a short period of time, treatment options, even if they are not entirely unproven, are often desired by such patients. This is understandable, because at such a severe stage of illness, such as prostate cancer, possible extension of their lives with comfort is worth it to them, regardless of lack of evidence of proof of whatever treatment that may be advantageous to them regarding these issues. The FDA, however, claims authority on the treatment options of such patients, although that administration has proven itself over the years to be rather inadequate with its frequent drug recalls and black box warnings, and they do these things only under pressure from the public, usually. Reform has to start somewhere at some time.
Prostate cancer is a rather frequent occurrence- with between 10 to 20 percent of men predicted to acquire the disease during their lifespan, resulting in about 30,000 deaths a year from this disease of the one million men. Furthermore, out of all cancer types more are dying from prostate cancer now than other cancer diagnoses.
For those unaware, there are different stages of prostate cancer, and the more severe the prostate cancer cases are which is determined by such methods as bone scans and Gleason’s scores, which is a score that assesses prostate tissue after it is biopsied and if it is determined that the stage of cancer is severe by this and to estimate proper treatment options if proven to be malignant. Typically, the initial suspicion of prostate cancer is determined by the results of what is called a PSA blood test, as PSA is a protein produced by prostate cancer cells. If the PSA blood test is above normal limits, a prostate biopsy is performed to determine and confirm not only the presence of cancer, but also the severity of the disease on such a patient.
Yet fortunately, and as you will read, innovation still exists in medicine. A few years ago, a small Biotechnology company called Dendreon was working on a conceptually new treatment for the worst prostate cancer patients, and this treatment therapy created by Dendreon was named Provenge. Provenge is the first immunotherapy biologic treatment for the progressed prostate cancer patients, and has proven to be a very novel and innovative treatment option for advanced prostate cancer patients who are terminally ill. Usually, these patients are unresponsive to usual treatment methods for prostate cancer, and are left with chemotherapy as their only treatment option at such a traumatic stage of prostate cancer. Understandably, most patients at this stage refuse treatment entirely, largely due to the brutal side effects of such chemotherapy treatments as taxotere. The immunotherapy method developed by Dendreon required the removal of white blood cells of the diseased patient and, after altered, are re-injected into this patient now designed to attack what is called PAP, which is on prostate cancer cells only. This treatment required only three such injections in a period of six weeks. This resulted in life extension twice that of chemotherapy treated prostate cancer patients of this severity, and without the concerning side effects of chemotherapy. The medical community and survivors of prostate cancer were elated and waited with great anticipation for access to this treatment method.
Fortunately, as the years passed, Provenge, by 2007, had convinced others of its safety and efficacy in its benefit for severe prostate cancer patients. This caused great joy to such patients and their families. Perhaps greater elation was experienced by the caregivers and specialists of such a disease, such as Urologists and Oncologists who treat such patients. While Provenge was on fast track status at this time at the FDA, the FDA panel thankfully recommended with clarity the approval of Provenge based on its proven and substantial efficacy and safety demonstrated in its performance in past trials. The FDA announced this to the public in the early Spring of 2007, I believe.
Now for the bad news: With great shock and surprise, the FDA agency rejected the approval of this great treatment for very sick patients due to, they said, ‘lack of data’ in May of 2007. This contradicts their favorable opinion of Provenge weeks before delivering this terrible news. Especially when one considers the FDA Commissioner is a prostate cancer survival himself!
Soon after this judgment was passed by the FDA, conflicts of interest were discovered by others. For example, a member of the FDA agency who was evaluating Provenge, Dr. Scher, was found to have a financial commitment to a future competitor of Provenge that was being produced by a company called Novacea, and this company had signed a co-promotion agreement with Schering with this similar prostate cancer drug being developed by this company. Dr. Scher never disclosed this conflict during the approval process of Provenge. As it turns out, this anticipated prostate cancer drug made by Novacea was discovered to have serious flaws, and Schering pulled out of the agreement with Novacea. In addition to this incident and before May of 2007, baseless letters were anonymously delivered to the FDA stating negative qualities about Provenge that were without Merit and speculative claims about the treatment. Yet overall, the disapproval by the FDA of Provenge angered many, and a newly formed advocacy group called Care to Live filed a lawsuit against the FDA for their clear lack of protocol or knowledge about such complex treatment agents as Provenge at the end of last year.
Terminal patients, I surmise, desire comfort during their progressive disease that has placed them in the last chapter of their lives, and certainly should have a right to choose any treatment that possibly could benefit them. At this stage of such a patient, one could argue, safety of any treatment option is not of concern to these patients, because they are going to die anyway. Yet the FDA, with reckless disregard and overt harshness for these very ill patients, ultimately harmed others more by not approving Provenge with deliberate intent.
The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge, and why they have not expanded this approval process to all terminally ill patients remains completely unknown. What is known is that they are harming those they pledged to protect so long ago by depriving such patients in need of treatment, as no other options are viable presently that are as safe and effective with great tolerability associated with Provenge. So now the FDA appears to be a bought, corrupt, and incompetent administration without loyalty and dedication to the public and its health. This needs to be corrected in any way possible for the lives of others. A terminally ill patient has a personal right to obtain and access such treatments upon their own volition as well as the discretion of their doctor, just as a terminally ill patient is granted an individual right to die, if they choose to do so. It is an individual decision in such cases that should be void of interference from others.
“Politics is the systematic organization of hatreds.” — Henry Adams
Dan Abshear
Author’s note: What has been written is based upon information and belief
Frank
One of the two committee members who opposed provenge said she did so because if provenge was approved DNDN would not be able to populate the placebo of any ongoing trials. INSANITY!!!!!!! or Corruption?????? I have no idea but its nuts and very typical of a federal government that is broken at every level.
Seeks the Truth
So the depth of the of the effort to subvert the approval of DNDN’s Provenge continues to be revealed. And the immense armor plate installed to protect the “agency” against public scrutiny continues to astound this citizen who assumed the agencies were founded to SERVE the citizens.
Meanwhile, TENS of THOUSANDS of men DYING of late stage Prostate Cancer have been deprived of a revolutionary vaccine that was judged to be both SAFE and EFFECTIVE, according to the governments own panel of acknowledged experts.
Where did the stinking slime originate and how much TRUTH has been smothered by the ooze??
Has everyone been so anesthetized by the daily revelations of crime and corruption in our once great nation that they can ignore this compelling story of graft, greed and conflicts of interest??
I thank my God for the few vilified “investors” who Seek the Truth in exposing this incredible abomination of moral and ethical behavior.
Lorine
“The battle has been largely ignored by the mainstream press and a Congressional committee declined to investigate, partly because the FDA has the right to request more data before issuing approvals and some believe the fight is really driven by angry Dendreon investors.”
It shouldn’t matter who is driving the fight to right a wrong. If there were shenanigans going on to derail Provenge, which it sure looks there were, wrong is wrong.
Tony F
Nice update on the Provenge tragedy, Ed!
Isn’t it interesting that the NCI–which had NOTHING to do with Provenge or the FDA Advisory Committee–has people involved in working AGAINST the approval process for Provenge?
Why?
Nice to see you once more mention the two alleged FDA AC members–Maha Hussain of University of Michigan and Howard Isadore Scher of Sloan Kettering, both of whom are well-known chemo researchers and prescribers–and their conflicts of interests.
For the new readers, Scher–in order to qualify to sit on the FDA AC panel in judgment of Provenge–certified to the FDA that he had 3 (Three) Conflict of Interests.
Net research suggests that, in actuality, he has at least 17 (Seventeen) COI. Those found are:
1. NOVACEA: Grants & Research support;
… STUDY CHAIR of DN-101
… a DIRECT competitor to Provenge
… DN-101 failed its clinical trial
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; 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. AMBRILIABIOPHARMA INC: Principal Investigator PCK3145, Phase I/II
16. MEDIVATION, INC: Principal Investigator MDV3100
17. PROQUEST INVESTMENTS,
… Board of Directors
… Advisor
… INVESTED in Novacea.
Of course, this info has been provided to Heath & Human Services Investigative division and the FDA Investigative Office and neither, to date, has looked into these allegations of illegality… are we surprised?
For shame on the FDA and the NCI for fighting against a treatment for a terminal cancer just because it potentially invalidates their own work.
What about thinking of the dying cancer victims instead of ones career?
Keep up your drums beating to expose these wrong-doings, Ed!
Barbie
After reading the letters Care To Live obtained throught Freedom of Information Act, I am amazed at the censorship of information.
Should it be renamed to the Freedom of Censored Information Act?
It is clear to me that this decision to withhold marketing approval for Provenge went far beyond Dr. Scher innocently voicing his concerns. Rather he involves many like mined RECIST old guard and self serving staff from NCI to collaborate in denying Provenge approval.
Dr. Scher appears to have been central to derailing Provenge. Is his conduct reasonable for advisory panel doctor? Dr. Francesco Marincola, who himself participated in the Provenge AC, stated that his role as a 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.”
MyPharmalotID
Dr. Marincola conducted himself as a true professional, by every definition of the word.
Now consider these facts:
Dr Scher was co-lead on the Phase III trial of Novacea’s (NOVC) drug for prostate cancer, Asentar, at the time of the Provenge advisory committee (AC) meeting. This drug would have competed with Provenge in the PCa space.
He also, at that time, was a scientific advisor to ProQuest Investments (”Proquest”), a venture capital firm in Princeton NJ.
Some Web sites showed Dr. Scher also to be an officer and member of the board of directors of ProQuest at the time of the Provenge AC meeting (March, 29, 2007). These Web sites no longer are available on the Internet, but have been taken down by party or parties unknown.
ProQuest Investments, at the time of the Provenge AC, owned slightly in excess of 8% of NOVC.
ProQuest Investments, at the time of the Provenge AC, had one of its officers serving on the NOVC board of directors.
At the end of May, 2007, three weeks after the FDA sent Dendreon its Complete Response (CR) letter (the FDA sent its letter to DNDN on May 8, 2007), Schering-Plough and NOVC signed a co-development deal for Asentar valued at $440 million. This contract surely was in the works for more than 6 months and, most likely, nearly a year. Furthermore, the boards of both companies would have had to agree to its terms. (Some months after the signing of the co-development deal, the Asentar Phase III trial was stopped because of the high death rate in the Asentar arm; Schering-Plough subsequently terminated the co-development deal with NOVC.)
Draw your own conclusions.
LILLI
Hundred thousands are dying from complications from cancer medications. Pharmaceutical Companies are really not interested in our health. Pharmalot is like an accident about to happen, only it is a promotional advertisement about to happen. Oncolgy news predicts cancer medications will outsell the Blockboster drug STATINS by the 2011. Why do they expect more people to get cancer? Why not pursue preventive medicine? But that would not sell medications and fill the greedy with money and power.
CMC guy
Donahue states “The fact is that the FDA has never stated an official reason why they denied approval to the Provenge (application).” Has the “approvable” letter ever been published by Dendreon? If it was a “Complete Response” as implied above then would have contained what was lacking for approval. I have seen press releases with statements but never the full picture presented. It is up to companies, not FDA, to release communications of this type.
The sad story seems to be largely from poor sponsor actions: Two Failed Pivotal trials occurred as Phase 3s did not meet the primary end-points. Proposing to gain approval on a gold standard end-point not even designed as secondary measure in the studies and then “demonstrated” by post-hoc statistical analysis. While I think other considerations warranted in the case (but not generally part of FDA process I believe) due to lack of options for these patients most other companies would have fully expected that more complete and focused data would be required beyond such as shaky submission. That seems to be the true part of this story that is being over looked.
Kerry Donahue, Esq.
CMC guy
Dendreon does not have to produce the CR letter for the FDA to disclose its reasons and process for declining a license to Provenge. It’s another red herring.
It did have to produce it for in camera review by the lower Court but the lower Court did not ask for it, instead relying on PR statments by Dendreon (so maybe it should have relied on Dendreons PR that said they proved safety and efficacy yet the application was denied due to “human nature” at the FDA”, as well.
The patients and their families have a right to know. The FDA is the public agency owing an explanation to the public not Dendreon.
Did you ever wonder why Dr. Pazdur has never denied the allegations made by CareToLive and has refused to respond to the FOIA.
Your so called scientific arguments have already been widely refuted and seen to be completely without merit.
CMC guy
Mr Donahue your statement asked “why” which I presume is in the letter that never has been published (as far as I know), so again up to Dendreon to provide that as today’s post elaborates since FDA bound by confidential nature (there was suggestion of CMC issues so I am particularly interested). I do not know but the additional questions of process are also likely closely linked to interactions with company/data that again would seem to be covered by confidentiality.
You and others seem operate by continued innuendo, intimidation and conspiracy theory. If you wish to dispute the science involved it seems clear to me. Provenge Two Pivotal Studies Required, Two Failed Pivotal Studies Failed (based on chosen endpoints). Backend salvage by modified statistically analysis shows promise but methods are debatable so would appear to have merit when FDA request additional data necessary.
Again I wish Provenge had been approved based on the target patients need even with limited benefit of a few months (and lack of side effects) but I can also imagine the howls of approving a drug based on inability to met primary or secondary endpoints.