Provenge Protesters Plan Ad Blitz On DC Buses
15 CommentsBy Ed Silverman // November 2nd, 2007 // 11:05 am
Angry and frustrated that the FDA still refuses to approve the Dendreon prostate-cancer vaccine, an ad-hoc group of cancer patients and investors is planning to sponsor ads on Washington, DC, area buses that may appear as early as next week, according to sources familiar with the effort.
The hope is to raise awareness among members of Congress and the public at large, and pester the agency, since FDA officials ignored a protest two months ago in front of the agency’s Rockville, Maryland, headquarters. The gambit is the latest among a series of actions - including a lawsuit against the FDA and YouTube videos - to generate a groundswell of sympathy and outrage in hopes of forcing the FDA to change its collective mind. (The organizers of the bus ads have declined to make a sample available, but we will post an image when we obtain a copy).
For those who don’t recall this complicated tale, an FDA advisory panel earlier this year recommended approval, but before the agency acted, two docs on the panel took the unusual step of writing the agency and urging a go-slow approach. Since then, the docs received threats amid accusations of undisclosed financial conflicts of interest and charges that an FDA official prompted them to write the letter as part of a behind-the-scenes power play. You can read details in the lawsuit.
Whether a series of bus ads will change anything is unclear. If not, the question then becomes what do the self-described disenfranchised do next?
Tony F
Ed,
It’s TGIF and many people are looking forward to the weekend working to clean up the last of the week’s work. I’d like to add a few items of clarification about the DC Ad Blitz article you wrote to enable your readers who may not be fully conversant with this tragedy to have more info.
1. “Dendreon prostate-cancer vaccine”, Provenge, has been submitted to the FDA for approval in use by TERMINAL prostate cancer victims who have an average 18 months of life left. This isn’t for a toe-nail fungus or a “little shpritz” such as Plethora Solutions premature ejaculation medication you wrote about Wednesday.
2. The “ad-hoc group” is actually an organized not-for-profit, CareToLive, whose info can be found on the net at http://www.caretolive.com; as I understand it, membership includes more people than just “patients and investors”. It’s reported that physicians, companies, family and friends of cancer victims, grass-roots local groups, retirees, advocates for cancer victims and a plethoria of others are CareToLive members–not just patients and investors.
3. Very importantly, imo, are the two docs on the FDA Advisory Panel–Maha Hussain of Univ of Michigan and Howard Isadore Scher of Sloan Kettering in NYC–who apparently went over and above the duties of their Special Government Employee employment by writing supposedly CONFIDENTIAL and very negative letters to the FDA which were subsequently leaked and printed publicly in “The Cancer Letter”… a non-peer reviewed newsletter.
4. Additionally, it appears from internet research that Hussain and Scher have UNdisclosed Conflict of Interests they failed to tell the FDA about when they applied for waivers to sit in judgment of Provenge last March.
My own research suggests that, while Scher told the FDA he had 3 COI, Scher has 17 to-date that I’ve found including close ties to Mike Milken, the convicted felon and former junk bond king, and Milken’s Prostate Cancer Foundation as well as being rather intimately involved in Proquest, another organization with about 1 BILLION in funds to invest in prostate cancer where Scher appears to be involved as a fund’s executive as well as participating in research of cancer treatments involving funds from both organizations.
5. The alleged “death threats”. To date, no one–including the supposedly good docs, Hussain and Scher–have stated that these ALLEGED threats have been reported to law enforcement, although the media continues to print the story as if it is true. Has either/both reported such alleged “death threats” to police?
If so, where’s the report?
If not, why not?
Anyone receiving written death threats–at least one as an email as alleged by Scher–are very easily traced and the perp swiftly caught these days. Such threats have no place in society at all–let alone against physicians–be they conflicted or not.
Common sense also suggests anyone who has been threatened with death would make a police report and would check their vehicles every time they get in it for hidden assassins or, perhaps, a hidden bomb, their rear-view mirrors for being followed or other type of life attempt if these reports are genuine. I, for one, do NOT believe them simply because there has been no information that these threats have been reported, that they are/have been investigated or that they are, indeed, real. The facts simply do not add up to a valid story, imo.
Thanks for keeping this topic in front of the public; here’s hoping that the FDA will find a way to permit TERMINAL prostate cancer victims a way to have access to this treatment!
Chris
I have asked this before but can’t recall if anyone answered: Has anyone seen the data and is the evidence so compelling? I understand the other issue under discussion: I’m just interested to know how good this really is.
MyPharmalotID
Chris,
The FDA’s own Advisory Committee, on March 29, 2007, voted 17-0 that Provenge is safe and 13-4 that it demonstrates substantial evidence of efficacy, the Congressionally mandated FDA standard. That’s a pretty strong recommendation for approval.
Chris
Thanks ID. I appreciate the way the voting went: It’s the efficacy data I’m interested in more than the recommendation for approval. After all that is the minimum standard for any approvable drug - if the drug doesn’t meet that criterion it should not be approved. It’s intriguing me how much better is Provenge than other drugs in the field. It sounds from all the comments on here and the external activity that it offers very significant benefits over existing treatments but I don’t know on what basis these claims are based. Not to say it shouldn’t be approved - seems like it should - just trying to balance the frenzy with the facts.
Thanks
MyPharmalotID
By the way, while we are talking abou the infamous Scher letter to the FDA…the one that was leaked to The Cancer Letter, Pharmalot recently had this to say about that:
[http://www.pharmalot.com/2007/10/who-wrote-the-mysterious-provenge-letter/]
“In particular, the drama has centered on the origins of the letters written by the two panel members, Howard Scher and Maha Hussain, which some believe were orchestrated by Richard Pazdur, who heads the FDA’s Office of Oncologic Drugs and is now rumored to become the agency’s new safety chief. The non-profit, Care To Live, argues the letters underscore the notion that there was a concerted effort among some at the agency to scuttle Provenge, a move that would benefit rival products in which people tied to the panel members allegedly had various interests.
“A draft copy of one of the letters, which was obtained by the non-profit under a Freedom of Information Act request, doesn’t indicate that it was written by Howard Scher (see photo), a Memorial Sloan-Kettering Cancer Center oncologist, but the author identifies himself as the primary investigator for the Prostate Cancer Trials Endpoint initiative. Pazdur’s name also doesn’t show up. Nor does Martin’s name. The Care To Live attorney, Kerry Donahue, says he doesn’t have documentation to verify Martin’s involvement, but cites sources who led him to mention her in the latest motion.
“Martin didn’t respond to a telephone message or an e-mail. And it’s not clear why she would participate in writing such a letter. However, she is familiar with both Scher and Hussain. In March 2005, for instance, all three participated in an FDA oncology drugs advisory committee meeting. And a June 2004 National Cancer Institute progress report on prostate cancer mentions research funding to various projects, including one called Spores. Martin was a member of the NCI working group and Scher, in his capacity at Sloan-Kettering, was a Spores co-investigator. As noted, it’s a small prostate-cancer world, after all.”
So, it would appear that Dr. Scher had plenty of help writing his letter (as many believed almost from the time that the leaked letter was first made public by The Cancer Letter, based on the errors found as well as the letter’s syntax and wording). What surprised many was the recent discovery of an early, draft (v.3) of the Scher letter (which included significant editorial comments) on a computer in NCI that was uncovered by the FOIA request.
Just how ethical, moral, and/or legal it would have been for employees of the Federal government to assist Dr. Scher (who, by the way, was a Special Government Employee at the time of the Advisory Committee meeting) in creating a letter to express his “personal” feelings about Provenge has yet to be determined by the HHS Office of the Inspector General, or barring him, the Department of Justice. But it’s time that the Federal government stepped up to the plate and looked at the matter before the press blows the lid off this scandle and someone is forced to resign for not doing their job in the first place!
MyPharmalotID
Chris, the best I can do, I think, is point you to the transcript for the March Advisory Committee meeting. That way, you and other readers can draw your own conclusions from the data presented.
http://www.fda.gov/ohrms/dockets/ac/07/transcripts/2007-4291T1.pdf
Chris
Thanks ID - helpful. There are 433 pages so I just skimmed the efficacy section.
The statistician said “Data from two Phase III studies were submitted to support license application. Both studies failed to meet the primary endpoint, and also failed to demonstrate statistical significance for other pre-specified endpoints. The key efficacy evidence was based on the difference in overall survival between the two arms.”
I’m not trying to make a point here as I know this is a much bigger issue than picking over the data - people could live longer if this drug were available, as it seems it should - but as a layman I’m not seeing from that presented the powerful efficacy data I expected.
Again, my interest only and nothing more than that.
MyPharmalotID
I won’t use this venue to discuss these issues. They’ve been debated for months on the InvestorVillage MB.
http://www.investorvillage.com/iv1/smbd.asp?clear=1&mb=971&pt=m
If you’d like a good, succinct answer to your question, I suggest you register on that board, I suggest you Private Message “Ocyan” and pose your question to him. I’m sure he will respond. Here is but one posting by him that you might find interesting:
http://www.investorvillage.com/iv1/smbd.asp?mb=971&mn=138687&pt=msg&mid=2449044
The efficacy of Provenge has been demonstrated in a substantial amount of data. In AIPC, D9901 showed high statistical significance with 36-month survival rates 34% treatment vs 11% placebo. Even the small and flawed D9902a showed 36 month survival rates 32% vs. 21%. In ADPC, the phase-2 trials D9905 and P-16 and the phase-3 trial P-11 showed statistical significance PSADT. The confluence of data from all of these trials says that Provenge is a treatment that shows direct beneficial effect. The experts on the panel drew from their expertise to see through the statistical misses and focus on the clinical evidence to come to the correct vote 13-4. Among the scientists on the panel, the four panel members who voted no had the least/no research experience with immunotherapy.
Be well.
MyPharmalotID
Chris, I think the best thing to do is join the discussion on the Investor Village (IV) Message Board, and, perhaps, Private Message “Ocyan” to get the answers you seek:
http://www.investorvillage.com/smbd.asp?mb=971&clear=1&pt=m
But to your point, here’s one posting by their learned gentleman that may be of interest:
http://www.investorvillage.com/iv1/smbd.asp?mb=971&mn=138687&pt=msg&mid=2449044
The efficacy of Provenge has been demonstrated in a substantial amount of data. In AIPC, D9901 showed high statistical significance with 36-month survival rates 34% treatment vs 11% placebo. Even the small and flawed D9902a showed 36 month survival rates 32% vs. 21%. In ADPC, the phase-2 trials D9905 and P-16 and the phase-3 trial P-11 showed statistical significance PSADT. The confluence of data from all of these trials says that Provenge is a treatment that shows direct beneficial effect. The experts on the panel drew from their expertise to see through the statistical misses and focus on the clinical evidence to come to the correct vote 13-4. Among the scientists on the panel, the four panel members who voted no had the least/no research experience with immunotherapy.
Be well.
Tony F
Chris, I expect with a lot of reading you’ll find these bits of info:
1. When the trials were started, Provenge (which is an immunotherapy–not a chemotherapy) had TTP as a primary endpoint of the trial as did the chemo trials of that period. TTP (Time To Progression) was used as a surrogate endpoint among many PCa clinical trials as a primary endpoint in place of what has now become the “Gold Standard”–overall survival. At that time some 10 years back, overall survival wasn’t typically an endpoint.
2. At the end of 36 months, if my memory is correct, about 33% of the Provenge treated patients were still alive. Only 11% of the placebo patients were alive. This is a significant and important resultant of the treatment, imo.
However, because “survival” wasn’t a PRE-SPECIFIED endpoint of the trials, it was NOT considered in the evaluation of the trial and its data.
If you’ll check on YouTube, there are videos of 2 Provenge treated patients at the Sept 18th FDA Rally in DC. You should, in particular, watch the Bruce Tower video and hear him tell–in his own words–exactly what he has gone thru up to and including treatment with Provenge and how he continues to lead his life after suffering from PCa for 10 years or more. And, most importantly, how he’s living it today after treatment with Provenge.
3. In addition, an audit of the data from the trials was made and errors in the tabulation were discovered which permitted the statistical significance of the data to come in at about a p value of 0.052. The “cut off” in p value data by the FDA is fixed at 0.05. Therefore, as I understand it, Provenge missed being statistically approved by the FDA by a mere 0.002 percentage points….
The FDA used the UNaudited and UNcorrected data and came up with a p value of about 0.082… significantly higher than the p value threshold of 0.050
4. Typical side effects of the treatment experienced by about 25% of patients, from my readings, is reported to be flu-like symptoms for 1 or 2 days following infusion.
As we know, the only approved treatment is the chemotherapy of Taxetore which has a death rate from the TREATMENT of 1 to 2% of patients. In addition, side effects of the chemo include–but not limited to–finger and toe nails falling out; hair loss; red blood count plummeting requiring medication to correct; hospitalization; tiredness; chills and fever; loss of appetite and so on… this chemo is a really tough treatment on men whose bodies are already ravaged by cancer.
It is also widely reported that 50% or more of men whose physicians advised Taxetore treatment refuse to take it because of these horrible side effects. Reports state they prefer to live their remaining life in as good of quality of life as they can have with their families.
5. Quality of Life: Obviously, men taking Provenge are reporting feeling better, having more energy and there are reports from people such as Edwardo Garcia (his testimony at the March 29th Provenge AC hearing is detailed in the hearing transcript) have lived about 8 years since Provenge treatment. His testimony is compelling and is a must read to hear from he and his family members who made the effort at their own expense to attend and speak in favor of Provenge.
I’m sure there are more items people can add to help you out in your quest for Provenge data. I think it of intense interest that there has been a clearly defined survival advantage to Provenge; unfortunately, “survival” wasn’t a pre-specified end point in the trials.
Lastly, the treatment demonstrates it is safe. So the question is why will the FDA “not” Conditionally Approve it allowing tens of thousand of PCa victims access to this safe treatment while collecting added data. The FDA can–at any time–terminate sale of the treatment in the event anything untoward or unexpected comes up while allowing those condemned to die from PCa a chance at a longer, better quality of life.
83 men die each and every day from prostate cancer; this is both a huge loss of life that, I believe, can be prolonged with Provenge and it’s a huge loss to the families of these terminal cancer men.
Lucy
Chris,
The Provenge survival data shows that the patients that received Provenge had longer median survival (4.5 months) than that reported for Taxotere therapy (the only FDA approved therapy for HRPC), without having to endure 7 months of infusion therapy and coping with the poisonous toxic side effects related to Taxotere infusion. I know that 4.5 months does not sound like a significant survival benefit, but in comparison, Taxotere was approved by the FDA for HRPC when it only demonstrated an increase in median survival by only 2-3 months. Half that of Provenge! In further support of its efficacy, a direct correlation between Provenge induction of an immune response and a survival benefit was also demonstrated in these patients. Also impressive is the fact that the data also showed that when Provenge treated patients were subsequently treated with Taxotere, their median survival almost doubled over placebo patients (from 20 months for placebo patients to 35 months for Provenge/Taxotere treated patients). This is compelling survival data further supporting the efficacy of Provenge for hormone refractory prostate cancer. The increase in survival from combined treatment is so dramatic and remarkable that it could not have been due to a random chance. This is amazing data and highlights just how powerfully effective Provenge is as an adjuvant to Taxotere, the existing standard of care, and/or Taxotere as a powerful adjuvant to Provenge. The study stopped after 3 years. However, many of the Provenge treated patients are still alive after 6 years and not included in the final survival statistics.
Furthermore, the primary endpoint for the pivotal Phase 3 trial was time to progression (TTP). The p value for this endpoint, according to the company, was 0.052. A miss of only .002. The fact that Provenge extends life but has a delayed effect on TTP is an axiomatic conundrum for the FDA’s CDER members and why the expertise of CBER panel members must be relied upon. This fact was recognized in a July 1st National Cancer Institute research report by Jeffrey Schlom, Ph.D., chief of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute.
Chris
Thanks everybody: Helpful info. Like most people, I suspect, cancer has directly affected my family - and I have also worked in and around the pharma industry for many years, including with the stats guys. I have witnessed the powerful effects exerted by patient advicacy groups on policy makers, so I think I can draw my own conclusions from what is presented both in the FDA transcript, interpreting that, and from the helpful comments here as to the real value of Provenge. I hope all who may benefit from it are in a position to do so sooner than later.
MyPharmalotID
Chris, please join us up on the DNDN InvestorVillage Message Board and join in the discussion. You won’t find a more dedicated group on the Internet.
Tom Smith
Question for the FDA when are you going to investigate Howard Scher’s COI’s?????? After all he did not claim Novacia/Proquest Investments. Why is he not being prosecuted for FRAUD???? I guess it will take lots of letter writing to the SEC, FDA, DOJ, Congress.
Tom Smith
Could the FDA be working for BIG CHEMO PHARMA to prevent Provenge approval?? After all they all know it works in late stage PC, but, I think what their really afraid of is it may just be a cure when given early on in the disease!! Yes a CURE for PC!!! This is the last thing BIG CHEMO PHAMRA wants approved because their sales of poison will go down the toilet!