Provenge And The Private Eye
11 CommentsBy Ed Silverman // August 10th, 2007 // 10:44 am
There’s nothing like the Provenge controversy to generate interesting tales. For those who don’t recall, Provenge is a prostate-cancer vaccine developed by Dendreon, and was recommended by an FDA panel last spring. But approval was unexpectedly delayed by the agency after two dissenting panel members wrote the FDA commish to think twice.
That set off a firestorm - threats and charges of conflicts of interest against the two panel members; protests by cancer patients; angry Internet missives by investors and, most recently, a lawsuit against the FDA filed by a newly formed non-profit called Care To Live, which appears to have been created specifically for this battle.
Now, the attorney who filed the lawsuit has posted details of how his private investigator stalked Paul Goldberg, who broke the story of how panel member Howard Scher wrote the FDA to delay Provenge approval. Goldberg publishes The Cancer Letter from his Washington, DC, home with his wife, Kirsten, who’s the publisher. The non-profit wants to know how Goldberg got the letter.
Two days ago, attorney Kerry Donahue took the unusual step of writing on the Investor Village web site: “Last night, the Goldbergs hid in their basement and refused to answer their door to accept CareToLive subpoenas. Today, they left town…
…in order to avoid further service (their counsel already acknowledged receipt of faxed subpoenas in this matter). Today they were served by personal process service on their household to a person over age 18. The Goldbergs thought they escaped town and avoided legal process. WRONG!
Apparently, their father, Boris Goldberg, lives with Paul and Kirsten (a household occupant over 18 years of age who can accept service). Our investigator followed Boris as he left the house tonight and he went to a restaurant. When Boris returned home to the Goldberg home/office, where he lives, our investigator said, “Hi Borisâ€. Boris responded with a ‘hello’.
The CareToLive Investigator then served Boris. At that time, panic set in with Boris and he said. ‘I am not Boris and I do not live here.’…The investigator got a good laugh out of the laughable attempt by Boris to say that he was not Boris and did not live there (third party sources have confirmed that grandpa Boris does live there).”
And why did Donohue post this? “The litigation is going to be expensive and needs to be funded,” he tells Pharmalot. “Everybody wants info. Something that has some excitement may encourage people to put some money up. This might help Care To Live raise more funding.”
Goldberg, so far, hasn’t returned messages left at his office or on his cell phone.
phil vardena
Hi Ed Silverman,
thank you for your nice job regarding Provenge.
I think you smell something, just like I do.
Those doctors that “leaked” letters (urging the FDA NOT to approve Provenge) to The Cancer Letter voted “NO” as to the effectiveness evidence that Provenge works. They were Dr. Sher and Dr. Hussain. (I let you judge on the ethics of this behaviour.)
On May 30, 2007, a couple of weeks after the FDA delaying letter, news was that Schering-Plough Corp. said it had agreed pay Novacea Inc. up to $440 million for rights to develop the smaller drugmaker’s prostate cancer treatment, causing Novacea shares to double.
Both Dr. Sher and Dr. Hussain are Novacea consultants.
Do you think Schering-Plough would have paid $60 million immediately and an additional $380 million to Novacea if Provenge was on the market?
Why the FDA - for the first time in its history - did not approve a drug deemed safe and effective by its own panel?
How is that Dr. Sher and Dr. Hussain - with their obvious and enormous conflicts of interest - took part in the panel?
Who did choose Dr. Sher and Dr. Hussain?
We already have proof that Provenge works (two phase III trials). Many people are going to die due to the delay. Who is accountable?
Why isn’t this revolutionary and extremely safe treatment available NOW?
I can’t imagine the motives are about monetary gains. Otherwise, this story is going to be huge!
Thanks again.
Bob Frazier
“FOLLOW THE MONEY”!!!!!
You can run; but, you can’t hid!!
Paul Haider
Ed,
An investigation is required into the matter of corruption and influence within the FDA, and in particular, the egregious handling of the matter pertaining denying immediate marketing approval to Dendreon’s Provenge for terminal prostate cancer. Certain detail is just not available in the public domain.
Provenge should have been granted immediate marketing approval by the FDA for men suffering from AIPC as recommended by the FDA’s own advisory panel. The FDA’s actions needlessly delayed access to a recognized SAFE treatment for 30,000 men annually. Forsaking survival of terminally ill AIPC patients for financial or personal gain is a morally reprehensible.
We should be seeking answers to the following questions?
1. Why were Dr. Scher and Dr. Hussain allowed to vote on the advisory committee (AC), much less participate, given their substantial conflicts of interest (COIs)? According to Pat Harley, Consumer Safety Officer at the Center for Biologics Evaluation and Research (CBER), the advisory panel for Provenge was initially planned to be composed of only of the CBER employees.
2. Did anyone ask Dr. Scher, Dr. Hussain or Dr. Fleming to write their letters to the FDA? What was the motive in having these letters written and in mounting what clearly was a major PR campaign to sink Provenge approval?
3. Did Drs. Scher, Hussain, and Fleming receive any assistance in the development of their letters? If so, who assisted them? Were any of the people who assisted them associated with companies that are competitors of Dendreon in the prostate cancer space? Were any of the people who assisted them associated with financial institutions that held positions from which they would benefit if Provenge were denied marketing approval?
4. Are the policies, processes, and procedures within the FDA adequate to address what appears to be an egregious example of conflicted interests on the part of Dr. Scher? My understanding of FDA policy is that the FDA will not publicly disclose non-public information provided by other participants without written authorization of the owner of the information, the written authorization from the individual who is the subject of the personal privacy information, or a written statement from the participant that provided the information that the information no longer has non-public status.
As Dr. Chuck Bennett so elequently stated, Dr. Scher’s participation in the Provenge advisory panel is akin to a defendant’s own sibling participating on a jury resulting in a hung jury decision. Knowing of Dr. Scher’s close professional relationship to ProQuest Investments, how is the public to believe that the FDA made the correct decision? Surely you can see the travesty of his participation in this matter. Such conflicts of public and personal interest jeopardize the legitimacy of one proclaiming to act on behalf of the public’s best interests.
Monica Sagen
Thank you Ed Silverman.
I have always been an advocate for the sick, and people who are less fortunate through circumstances beyond their control.
I was just an investor very interested in Dendreon (Provenge) not just because of the obvious (financial returns) but what Provenge could do for end stage PC patients and the potential to develop similar vaccines for other cancers.
After I joined Investor Village I began to see before my very eyes investors/patients/advocates wanting to make change after the FDA delayed the decision to approve Provenge.
We are Americans doing what we do best and that is standing up for our rights to make change for the better especially when we have to do it ourselves for humanity.
Remember, empathy is the ability to place oneself in the position of another living being and understand that person’s feelings.
Tony F
Barry Bonds best look out!
You’ve hit yet another Home Run in the apparently never-ending saga of the Provenge tale! Congratulations on getting this information and passing it along to your readers and to the whole World via the net! Prostate cancer victims everywhere have another reason to hope for an early, at least, Conditional Approval allowing these TERMINAL cancer victims access to a treatment which gives them excellent Quality of Life and appears to provide many with added life span.
For those new to this controversy and unaware of the alleged Conflict of Interests of one of the doctors on the Provenge FDA Advisory Committee meeting in March… here’s a recap on Scher’s, of Sloan Kettering in NYC, COI’s found on the net:
Scher seemed to represent to the FDA via his Feb 2007 Application for a Waiver to serve on the Provenge Advisory Committee that he has 1 stock ownership (between $5,000 and $100,000) and 2 “Grants (Related)” each between $100,000 and $300,000.
Publicly available information shows these apparent Scher COIs (so far): [Particular attention is directed to items 1, 2 and—especially--15, but ALL—in totality-- are important and telling, imo]
1. Novcea: STUDY CHAIR of DN-101; Grants & Research support
2. Medivation, Inc: PRINCIPAL INVESTIGATOR MDV3100;
3. Innovive Pharmaceuticals: PRINCIPAL INVESTIGATOR
4. Infinity Pharmaceuticals: PRINCIPAL INVESTIGATOR
5. Cougar Biotechnology: PRINCIPAL INVESTIGATOR; Advisory Board
6. Department of Defense: PRINCIPAL INVESTIGATOR PC Clinical Trials-P1 and P2
7. Bristol Myers Squibb: Consultant, Grants & Research support
8. Millennium Pharmaceuticals: Grant of Research support
9. sanofi-aventis: Grants & Research support
10. Genta: Scientific Advisory Board (as of March 6, 2007; since removed from web, but cached)
11. Biogen-Idec: Joint stock with spouse
12. Pfizer: Joint stock with spouse
13. Pharmion: Financial Conflict of Interest per Scher quote in MedPage
14. GPB Biotech: Financial Conflict of Interest per Scher quote in MedPage
15. PROQUEST INVESTMENTS: Consultant, Scientific Advisory Board; Limited Partner FINANCIAL interest
Go back and read #15 again…. He’s reported to be a “LIMITED PARTNER†in a Proquest partnership; doesn’t that suggest FINANCIAL investment?????
Cancer advocates will hold a Rally at the FDA in Washington on Sept 18th at 10 a.m. Details are at http://www.caretolive.com
Come and support cancer victims!
… and Thank You! for getting this tale told… another chapter has been written!
Michael
In all the excitement and fervor to find conspiracy, everyone forgets one thing: Provenge failed both its Phase III trials. Personally, I don’t want FDA approving drugs that failed to hit the designed endpoints in the two trials submitted to back the application.
Believe me, FDA is thick with the drug industry. But don’t forget that FDA turned down a non-cytotoxic cancer drug, with which it has little experience dealing with, and which was backed by a subpar approval package. Never mind that the efficacy question posed to the panel was changed to better facilitate approval — not your usual proceeding. But no one wants to talk about that — we’d all rather focus on conspiracy.
For those watching this story long before it got so juicy, it’s no surprise the FDA turned it down.
Jon
Michael….
The efficacy question was changed to reflect standards put in place by the FDA. Check out any other A/C meeting transcripts and see for yourself.
Speaking of conspiracies, who changed the question to “establish the efficacy”? and which Big Pharma do you work for?
From David Miller:
the original question posed by the Agency to the Advisory Committee at the meeting was: “Does the submitted data establish the efficacy of Sipuleucel- T (APC-8015) in the intended population?†The first 4 respondees on the Committee voted “no.†The question was then changed to: Do the data show “substantial evidence.†A series of “yes†votes followed.
The Federal Food Drug and Cosmetic Act passed by Congress in 1962 included a provision requiring manufacturers to establish a drug’s effectiveness by “substantial evidence.†A review of the panel meeting clearly indicates panelists were having a hard time trying to determine what level of proof was required for “establishâ€. The FDA correctly changed the question to reflect Congressionally-mandated approval standards.
During the panel meeting, Dr. Jesse Goodman, the Director of CBER, suggested the question change to Dr. Celia Witten, head of the FDA’s CTGT. Some accounts of the meeting inaccurately report the question was changed by Dr. James Mule, the Chairman of the CTGT Advisory Panel. The top two FDA personnel at the meeting changed the question to match the FA’s own regulations, not the panel itself.
Michael
Right, I know what the question was, and how it was changed. So, let’s recap: After the FDA sees four straight “no” answers on efficacy, and it seems this drug will not get a positive vote on efficacy, the FDA decides to lower the bar and reshape the question. Suddenly we have “yes” answers, and thus the vote went in favor for efficacy. Had the FDA left that question alone, the drug would not have received a positive vote for efficacy, and none of this hullabaloo concerning the FDA overturning a panel recommendation would have followed, and thus the cries of conspiracy lessened. It’s clear FDA does not know how to handle cancer drugs that are not cytotoxic — it was fumbling around midway through its own panel meeting.
But remember, I’m not saying patients shouldn’t have access to Provenge, or that it should not be approved. And I’m not saying conspiracies don’t exist, or that FDA isn’t full of holes. It is. All I’m saying is that the package supplied by Dendreon (and the history behind the drug) is not very solid. It seems to provide benefit to a sub-section of prostate cancer sufferers that was not the focus of either phase III trial. And beyond that, FDA does not know a lot about cancer “vaccines,” so if you want approval, you had better have a nice package. Dendreon didn’t.
Just putting it all in perspective. And no, I don’t work for big pharma. And I don’t work for a patient advocacy group either. I’m just a post-doc who can look at this logically.
Paul Haider
Michael,
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. The overall survival p value was 0.01. TTP is a substitute measurement for survival. According to a July 1st National Cancer Institute research report titled, Cancer Vaccines: Moving Beyond Current Paradigms, by Jeffrey Schlom, Ph.D., chief of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute, patients who received Provenge responded better to subsequent chemotherapy. Evaluation of cancer vaccine effectiveness based upon tumor regression is inappropriate and should be judged by different criteria than survival data from chemotherapy drugs. The fact that Provenge extends life but has a delayed effect on TTP is an axiomatic conundrum for the FDA’s ODAC members and why the expertise of CBER panel members must be relied upon. Furthermore, Provenge has much milder side effects than poisonous Taxotere chemotherapy, the only other treatment in terminal prostate cancer to show a statistically significant survival benefit. Additionally, a direct correlation between Provenge induction of immune response and survival benefit has also demonstrated and those patients who received Provenge did not have to endure 7 months of infusion therapy.
When Provenge treated patients were subsequently treated with Taxotere, their median survival almost doubled (from 20 months to 35 months). This is compelling survival data further supporting the efficacy of Provenge for hormone refractory prostate cancer. In comparison, Taxotere increases median survival by only 2-3 months. This increase in survival is so dramatic and remarkable, it could not have been due to a random chance. This clearly shows that Provenge is effective at extending overall survival from AIPC beyond any reasonable doubt. This is amazing data.
In light of the overwhelming need for better treatment options for 30,000 terminally ill androgen- independent prostate cancer patients, the unmatched safety profile of Provenge and the huge financial conflicts of interest of the panel Drs. Howard Scher and Maha Hussain, how is a reasonable person to believe the legitimacy of their over the top arguments proclaiming to act on behalf of the public’s best interests? Voting on and participating in an FDA advisory meeting in order to determine which drugs receive FDA marketing approval in which you play a decisive role in and in which you have a financial interest in (or counter interest in), is contrary to unbiased public concern and counter to the fiduciary duty Dr. Scher and Dr. Maha Hussain accepted as a special government employee and FDA panel advisor.
Provenge should be approve now! Cancer patients and advocates will be holding an FDA rally September 18th to raise awareness of the current situation and elicit change at the FDA. You can find out more at: http://www.arighttolive.com Please join us in support of cancer patients September 18th.
David Hamilton
Like Michael, I’m kind of bewildered by the level of conspiracy thinking this case entails. Dendreon took a variety of shortcuts in its phase III program, ended up with statistically unconvincing results from several fragmented patient populations in whom Provenge still failed the primary endpoint, and decided to heave the whole mess in front of the FDA anyway to see if it might slide by. The FDA dinged it, just as it does many companies who try to game the system, and said to come back with better data.
I’m also uncertain why people aren’t more interested in the fact that Dendreon CEO Mitchell Gold chose the day after the surprise advisory-panel vote to sell off a big chunk of his shares. It sure looks like Gold could read the writing on the wall.
As for conflicts of interest, I agree that FDA advisory panels shouldn’t allow them, although academic medicine is so close to industry these days that it does raise the question of who will actually serve on these panels if a strict conflict-of-interest rule is enforced. But it’s also worth thinking through what actually constitutes a “conflict,” and I don’t understand why consulting work related to non-active immunotherapy drugs necessarily represents a conflict to assessing a treatment like Provenge. After all, if Provenge works, it may well end up being used in combination with other agents, including cytotoxic chemotherapy like Taxotere or Novacea’s (experimental) Asentar. Heck, Provenge has already been tested in combination with Avastin (see http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16736512&query_hl=35&itool=pubmed_DocSum for details) — would that make a panel member conflicted if he or she had consulted for Genentech?
VentureBeat » Weekend update: That cold, cold artificial heart, Dendreon-related skulduggery, congressional earmarks, and more
[...] and the private eye — Pharmalot’s Ed Silverstein brings us the interesting tale of a plaintiff’s private investigator who stalked the editor of Cancer Letter, a newsletter [...]