On May 8, 2007, FDA Commissioner Andrew von Eschenbach refused to approve
Provenge for men with end-stage prostrate cancer and instead, issued a Complete Response letter to Seattle-based Dendreon, the vaccine's maker, requesting more data that may not be available until 2010.
Cancer patients and advocacy groups say intentionally delaying the approval of new therapies for terminally ill patients in order to protect profits in the research and treatment industry should be a criminal offense, and they are calling on Congress and the Security and Exchange Commission (SEC) to conduct a full investigation of the conflicts of interests involving the FDA officials responsible for the non-approval of Provenge.
As for the data requested by the FDA, an accurate assessment of the full effects of Provenge on survival can not be assessed easily because many of the participants in the clinical trials are still alive many years after they received the vaccine.
In a perverse twist of fate, because patients are living longer with a vaccine that works, it will take longer to provide the FDA with the data it requested.
Provenge is at the leading edge of a new class of cancer treatments that stimulate the body's immune system to fight cancer cells. The non-approval of the vaccine will not only shorten the lives of tens of thousands of men with end-stage prostate cancer, it will also have wide-spread negative effects for many patients because it could cause the biotech industry to slow development of immunotherapies that are being investigated for many other types of cancer, including breast, lung, ovarian, cervical, kidney, and colon cancer.
Provenge sought approval for men with androgen-independent prostate cancer (AIPC) who had already failed other forms of therapy. Experts say in all likelihood, Provenge works better than shown in prostate clinical trials because the vaccine was only tested on very sick patients with a large bulk of cancer cells and immune systems that already had been severely damaged by the disease itself and the toxic therapies they received.
If the vaccine were to be approved, patients in earlier stages of cancer with stronger immune systems would also have the chance to benefit from the vaccine.
The only treatment approved for late stage prostate cancer patients is chemotherapy with Taxotere (docetaxel), marketed by Sanofi-Aventis.
The FDA approved Taxotere in May 2004, in combination with the steroid prednisone, but for prostate cancer patients with limited life expectancy. However, the side effects of many months of chemotherapy outweigh the benefits in many cases, and most men opt not to undergo the treatment.
The cost of Taxotere is $2,500 a dose, according to the October 1, 2006, New York Times, while the average survival benefit is only about 2½ months. Between one and 2% of the men who receive the treatment die from it.
In contrast, the Provenge vaccine is administered 3 times over a period of 6 weeks with side effects occurring in only one of every 4 patients, usually consisting of mild flu-like symptoms that last one or two days. In a study that compared the vaccine to a placebo, after 3 years, 34% of the patients who received Provenge were still alive compared to 11% of the patients in the placebo group.
Provenge was designated for fast track approval under an accelerated process enacted by Congress to ensure that drugs that treat a devastating disease would become available more rapidly. The responsibility for reviewing and approving the Biologics License Application (BLA) rested with the Office of Cellular, Tissue, and Gene Therapies in the FDA Center for Biologics Evaluation and Research (CBER).
The major outrage over the non-approval of Provenge, stems from the fact that on March 29, 2007, the FDA's Cellular, Tissue and Gene Therapies Advisory Committee (AC) reviewed the BLA for Provenge and the 17 member panel recommended approval by an overwhelming majority.
On the issue of safety, the vote was 17-0. On the question of evidencing "substantial efficacy," the vote was 13-4 in favor of the vaccine. Needless to say, men with prostate cancer all over the US, and probably the world, were elated upon hearing the news.
The prostate cancer community has been waiting for the approval of Provenge for years. In the book, "A Primer on Prostate Cancer: the Empowered Patient's Guide," published by Life Extension Media, authors Dr Stephen Strum and Donna Pogliano listed Provenge as one of the promising "treatments on the horizon" five years ago in 2002.
Considering that the FDA could have approved Provenge as an experimental therapy as early as 2002, the agency's delay in approving this one drug alone may have resulted in the premature death of tens of thousands of men, according to the article, "FDA Rejects Promising Prostate Cancer Drug," by Dr William Faloon in a special 2007 edition of Life Extension magazine.
"In fact," he writes, "from the time of the release of the data on this drug in 2002, tens of thousands of American prostate cancer patients have died in the FDA's waiting room."
Everything that occurred during the public hearing on Provenge indicated that approval was a mere formality. The FDA had never overruled the recommendation of its own advisory panel to approve a treatment for cancer patients with no alternative but death.
Hopes were also raised earlier in the year, on February 9, 2007, when the FDA and the National Cancer Institute (NCI) held a groundbreaking seminar on immunotherapies titled, "Bringing Therapeutic Cancer Vaccines and Immunotherapies Through Development to Licensure."
The event was hosted by FDA Commissioner von Eschenbach, who summed up the theme of the seminar as follows: "Cancer vaccines and immunotherapy are ready to move beyond proof of concept studies, and we are ready to move them to the patients as safe and effective treatments for cancer."
"Therefore our primary focus," he said, "is to share our collective expertise and find solutions to the challenges of bringing cancer vaccines and immunotherapies through development to licensure."
But most importantly, for an agency that is often viewed as a roadblock to the introduction of novel treatments for life-threatening diseases, Dr von Eschenbach stressed that under his direction, the "FDA will be a bridge to the future, not a barrier."
It follows that the expectations in the prostate cancer community were high that Provenge would be approved in May 2007.
In addition, FDA officials have compounded the injury caused by the non-approval by steadfastly refusing to give cancer patients or the general public an explanation as to how and when the non-approval decision was made.
On July 30, 2007, Ohio Attorney Kerry Donahue filed a lawsuit in Federal court on behalf of CareToLive, a nonprofit association of prostate cancer patients, families, doctors, investors, and patient advocates seeking an emergency injunction to make the vaccine available to dying patients and alleging a conspiracy to sabotage its approval.
The defendants include FDA Commissioner von Eschenbach; Michael Leavitt, Secretary of the Health and Human Services Department; Dr Richard Pazdur, director of the FDA's Office of Oncology Drug Products; and Dr Howard Scher, an oncologist at Memorial Sloan-Kettering Cancer Center in New York, who is one of the members of the advisory panel who voted against approving Provenge.
On the taxpayer's dime, eleven US attorneys from the Department of Justice are listed on legal filings as representing the defendants in the case.
The lawsuit alleges that Dr Pazdur positioned Dr Scher and Dr Maha Hussain, a professor and researcher at the University of Michigan's Comprehensive Cancer Center, to serve on the AC to sway the vote against Provenge because he knew they both stood to benefit professionally and financially from a non-approval of the vaccine due to numerous conflicts of interest.
Dr Scher and Dr Hussain are considered experts in treating prostate cancer with chemotherapy, but neither has any expertise with immunotherapy. They are both deeply imbedded in the multi-billion dollar cancer research and treatment industry and their lucrative sources of income would no doubt suffer greatly if Provenge were approved.
Dr Scher and Dr Hussain are currently highly paid lead investigators for numerous clinical trials funded by companies that manufacture chemotherapy drugs and other new cancer therapies that are in direct competition with Provenge for the treatment of late stage prostate cancer patients.
In a September 5, 2007, Amended Complaint, CareToLive also alleges that Dr Pazdur "recruited and illegally used FDA employees" at and after the hearing to assist him in "wrecking" the Provenge BLA by requesting the preparation of anti-Provenge letters and designing a method for leaking them to the press.
When Dr Scher and Dr Hussain were unsuccessful in persuading the members of the AC to vote against Provenge, both sent letters to the FDA after the hearing, which they claimed to have written themselves, urging the non-approval of Provenge.
Both letters were leaked to, and published by, "The Cancer Letter," a non-peer-reviewed industry newsletter and a third letter, authored by Dr Thomas Fleming, a biostatistician from the University of Washington, was also sent to the FDA and subsequently leaked to "The Cancer Letter."
"Pazdur requested the letter writing campaign and designed the method for "leaking" them to the press," according to CareToLive's lawsuit complaint.
However, sources familiar with the case, now say that the leaked letter plan was developed at what they refer to as a "panic meeting" following the AC hearing and that Dr Alison Martin, of the NCI, was the main author of Dr Scher's letter.
The same sources say that another NCI employee, Dr Howard Streicher, also attended at least one meeting where Dr Scher's letter was discussed, and that Dr Streicher is in the position to expose what went on and who all was involved in the leaked letter plan.
By law, as a matter of due process, the FDA is required to post all briefing documents relative to the approval of a product under review that will be considered by the advisory panel on the agency's web site in advance of the public hearing for the benefit of all interested parties.
The FDA is also required to post a transcript on its web site for all public hearings to document what occurred. And here's where the plot thickens. The AC met on March 29, 2007, and the FDA released a 6-part audio tape of the hearing on April 4, 2007. Part six contains the voting of the panel members, but Dr Scher's safety vote is completely left out of the tape.
A written transcript of the hearing was released on April 13, 2007, the same day that Dr Scher's letter was published in "The Cancer Letter," but his safety vote is also missing in the written transcript. When the court reporter was contacted by CareToLive to ask why Dr Scher's testimony was missing, the reporter stated "talk to the FDA," according to sources familiar with the case.
A September 10, 2007, CareToLive brief says the panel's recommendation to approve Provenge, "caused co-conspirators Dr. Pazdur and Dr. Scher to go into panic mode as it is believed they were prodded by the devastated financial investment community they were involved with, after Dr. Scher and other insiders assured them that Provenge was not going to obtain approval."
The legal brief notes that certain investors were upset because "based on the inside information they had were either "short the stock" as Dendreon had a nearly unheard of 40% "short" interest; or were invested in direct competitors of Dendreon's Provenge."
Feeling the pressure, the brief states, the conspirator's recruited Dr Hussain and Dr Fleming to "wage a campaign against Provenge to depress its stock value and to lobby both the public and the decision makers at the FDA."
"Short sellers" are investors who bet that a stock price will fall. In the case of Provenge, the short-sellers could have potentially lost hundreds of millions of dollars if contrary to their insider information, the FDA followed the recommendation to approve Provenge.
On April 13, 2007, Dr Scher's letter appeared on the internet in "The Cancer Letter." On April 26, 2007, Dr Hussain letter was made public by same source, and on May 4, 2007, the third letter by Dr Fleming magically appeared on the internet via The Cancer Letter."
Five days later, on May 9, 2007, when the news came that the FDA would not approve Provenge, shares of Dendreon stock dropped from $17.74, to finish the day at $7.31, and the short sellers made out like bandits.
On November 26, 2007, CareToLive issued a press release to announce that the lower Court had dismissed the lawsuit, but that an immediate appeal would be filed in the 6th Circuit Federal Court in Ohio where the case will be reviewed by a 3 judge panel.
Mr Donahue says he believes that he can get a tight briefing schedule from the sixth circuit case manager that could put the decision in that Courts hands within 60 days.
CareToLive is also consulting with Mr Donahue and other counsel, about filing individual lawsuits against Dr Pazdur and Dr Scher in their home states, according to sources familiar with the case.
A sign-on letter is available on the CareToLive web site at http://caretolive.com/ for persons who want to join the effort to urge Congress to investigate the Provenge matter.