On February 13, 2008, Congressman Dingell’s House Committee on Energy and Commerce responded to the call for hearings in the matter of conflicts of interest (COIs) regarding how the FDA handled Dendreon’s (NASDAQ:DNDN) application for Provenge by rejecting the request on the basis of two arguments:
- “FDA has not yet made a final decision on this product, and it is the practice of this Committee to allow a regulatory agency such as FDA to complete its statutorily-mandated processes and render a final decision before initiating formal investigative action.”
- “A preliminary investigation into the record of the March 29, 2007, Open Session of the Cellular, tissue and Gene Therapies Advisory Committee that reviewed Provenge shows that the two advisory panel members you mentioned in your letter [Dr. Howard Scher and Dr. Maha Hussain] were granted waivers in compliance with the conflict of interest rules in force at that time.”…”Importantly, since the advisory panel that considered Provenge met, a new law strengthening conflict of interest provisions now governs FDA advisory panels.”
Unfortunately—and in what should be a major embarrassment to Mr. Dingell and his Committee—neither statement has anything to do with the original request for hearings! Clearly, for whatever reason, the Committee was given a flawed recommendation…one that not only ignored the bases for the request for hearings, but the evidence as well.
In their original letter of December 13, 2007, to Mr. Dingell, et al., Hon. Michael Michaud, Dan Burton, and Tim Ryan noted that:
Prostate cancer activists have raised questions about two of the negative voters [at the March 29, 2007, Provenge Advisory Committee [AC] meeting], academic medical oncologists Maha Hussain and Howard Scher. Dr. Howard Scher is lead investigator for a competing cancer drug made by Novacea and is listed as an adviser to a large venture capital firm that is also a major investor in Novacea. We believe the FDA should not be appointing scientists leading the testing of a rival drug for another firm onto the advisory committee evaluating Provenge nor should the FDA appoint an adviser to a large investor in such a competitive firm as a panel member. It is important that Congress examines possible ethical violations of these panel Members considering the viability of potentially important life-saving drugs.
Simply put, the three congressmen (and other congressmen who supported them) were asking the Committee to investigate the COIs of Drs. Hussain and Scher. They were not asking the Committee to force the FDA to approve Provenge; protocols already are in place to address that issue later this year or in 2009.
As to the waivers granted, citing the fact that a new law strengthens COI provisions basically closes the door after the horse has left the barn. The fact is, if the FDA had acted in good faith prior to the Provenge AC meeting, it would have rejected Drs. Scher and Hussain’s waiver requests. A study published by BioCentury, The Bernstein Report On BioBusiness®, March 26, 2007, noted the following:
Under the draft guidance, Scher either would be prevented from voting or excluded from the meeting.
As regards to Dr. Maha Hussain:
The waiver notes that Hussain is the principal investigator on a research contract awarded by a competing company for a product that is not related to Provenge. Under the draft guidance this probably would not be considered a conflict. However, the fact that her husband owns stock in three competing companies, valued at $15,000-$300,000, would at minimum prevent her from voting. If the total value of the stock exceeds $50,000, Hussain wouldn’t even be at the table if the new policy were in effect.
Vince Tolino, Director, Ethics and Integrity Staff, FDA, should never have forwarded Scher’s and Hussain’s waiver requests to Randall Lutter, Ph.D., Associate Commissioner for Policy and Planning, FDA, and the latter never should have approved them.
Mr. Michaud, to say the least, was angry with the House Committee’s decision. In a statement released late Wednesday to The Hill, he said:
I am deeply disappointed with the Energy and Commerce Committee's decision. I don't think this is the end to the issue. Congress needs to get to the bottom of this. I am exploring other possibilities to bring attention to this serious matter.
That the House Committee on Energy and Commerce could not grasp the depth of the COIs defies logic. There is no question that the waiver requests were flawed. But other issues cry out for investigation, including:
- Who asked Dr. Scher to write his infamous letter to the FDA shortly after the favorable March 29, 2007, AC meeting, disparaging Provenge. (There is anecdotal evidence based on conversations at a cancer symposium last summer to support this contention.)
- Who helped Dr. Scher write his letter to the FDA? At least one draft of Dr. Scher’s letter (v.3) was found on a PC in NCI, and at least one NCI employee attended a meeting called at the FDA to discuss this letter. (Source: NCI FOIA requests)
- Who leaked the letters written to the FDA by Drs. Scher, Hussain, and Fleming, disparaging Provenge, to The Cancer Letter? Interestingly, Dr. Scher’s letter was addressed to the FDA Commissioner Andrew von Eschenbach, MD; the formal salutation is crossed out and the name “Andrew” is written across it in pen. This is the same letter that Dr. von Eschenbach denies ever receiving. (Source: FDA FOIA requests)
- At the time of the Provenge AC meeting, Dr. Scher was the co-lead on Novacea’s Phase III Asentar drug trials for prostate cancer…a drug that was being developed in direct competition with Provenge. What impact did this have on Dr. Scher’s judgment and activities during and in the months following the AC?
- One Internet source shows that Dr. Hussain is on the advisory board of, and is a consultant to, Novacea. What impact did this have on her judgment and activities during and following the AC?
- Dr. Scher is on the Scientific Advisory Board of ProQuest Investments, a healthcare venture capital firm. At least one Internet source also shows him to be an officer and a member of the board of directors of the same firm. At the time of the Provenge AC meeting, ProQuest Investments owned in excess of 8% of Novacea. What impact might this have had on Dr. Scher’s judgment and activities during and in the months following the AC?
- Just 3 weeks after the FDA sent Dendreon a Complete Response (“Approvable”) letter, Novacea signed a $440 million co-development deal for its late stage prostate cancer drug, Asentar, licensing product rights to Schering-Plough Corporation. Deals such as this can take up to a year or more to develop and mature. All of which leads one to ask: Who knew what, and when did they know it?
Questions abound. But none, perhaps, is more important than this one: Who is looking out for prostate cancer patients, advocates, families, and investors in this case? The Office of FDA Ethics? House and Human Services’ Office of the Inspector General [HHS OIG]? GAO Fraudnet? The SEC? (By the way, inquiring minds would like to know why the short interest in Dendreon (DNDN) went up following the favorable Provenge AC meeting, and why Dendreon still is on the SEC’s RegSHO list.) The DOJ?
As of today, more than 23,000 men have died of prostate cancer since May 8, 2007, the date of the FDA’s Complete Response letter for Provenge. That number is over 4 times the number of US and Allied combatants killed in Iraq and Afghanistan since the beginning of the war. And the death count for prostate cancer in the U.S. continues to mount at the rate of 83 per day.
Clearly, the House Committee on Energy and Commerce didn’t have a clue as to the path it should have taken in this matter. Which brings us to Alice in Wonderland:
Alice: Would you tell me please, which way I ought to go from here?
Cheshire Cat: That depends a good deal on where you want to get to!
Alice: I don't much care where.
Cheshire Cat: Then, clearly any path will do.
–Excerpt from Alice's Adventures in Wonderland (1865), by Lewis Carroll
Disclosure: Author has owned shares of Dendreon since 2006