The defendants in the lawsuit include the FDA Commissioner, Dr. Andrew von Eschenbach, his boss Mike Leavitt, Secretary of the US Department of Health and Human Services, Dr Richard Pazdur, head of the FDA's Office of Oncologic Drug Division, and Dr Howard Scher, hand-picked by Dr Pazdur to serve on the advisory committee.
Other conflicted panel members include Dr Maha Hussain, a professor at the University of Michigan, and Dr Savio Lau-Ching Woo, a professor of gene and cell medicine at Mount Sinai School of Medicine.A law was passed back in November 2005, that required members of committees to disclose all financial ties to the pharmaceutical industry and the categories for disclosure were broken down into dollar amounts with time frames, such as less than $10,000 a year or between $10,000 and $50,000 a year.
However, as usual, a major loophole remains where FDA officials are permitted to grant waivers to panel members even when they do have extensive financial ties to drug companies. Six month after the law went into effect, on April 21, 2006, the Boston Globe reported on the actual effects of the law and determined that the FDA had granted close to 100 waivers in less than 6 months.
Apparently, Provenge (known technically as Sipuleucel-T) is but one of many cell and immune-based therapies that have been under development over the past decade. However, the Seattle-based Dendreon is the first to seek FDA approval for a product in this new class of immunotherapy for the treatment for androgen-independent (hormone-refractory) metastatic prostate cancer (AIPC).
The immune system defends the body against infections and diseases, and the Provenge vaccine is designed to stimulate the patient's immune system to attack cancer cells in the same way that it attacks bacteria or viruses. The entire course of treatment involves 3 donations of blood over a brief period of time, each of which is processed by Dendreon and then sent back for infusion into the patient.
A study submitted by Dendreon to back the approval of the vaccine showed that after 36 months, 34% of the men who received Provenge were still alive as compared to only 11% of the group who received a placebo, or a 23% difference.
Currently, the chemotherapy drug Taxotere (docetaxel), made by Sanofi-Aventis, is the only FDA approved drug for the treatment of AIPC.
Many patients and patient advocates testified at the March 29, 2007, hearing, and some literally begged the FDA to approve Provenge. Joel Nowak, 56, traveled from Brooklyn to testify as a patient and a as representative of the advocacy groups "Raise a Voice" and "MaleCare," for which he serves as the program director for advanced prostate cancer.
Mr Nowak was diagnosed with recurrent advanced prostate cancer in December 2005, and said, according to the National Cancer Institute, the expected mortality rate for advanced prostate cancer is over 50% within 36 months of diagnosis.
"If you take the statistical next step," he told the panel, "since I've already exhausted 16 of those months, which means I may have only but 20 months left to be on this Earth."
He noted that treatment choices are fairly non-existent. "Those of us who suffer with advanced prostate cancer have already gone through the mill of barbaric treatments," he told the panel.
"We've had our prostates removed or radiated, often leaving us with varying degrees of incontinence and impotence," he said, "and then 30 percent of us suffer a recurrence."
Mr Nowak explained that this signals the beginning of the clock's final countdown and described the desperate attempts by cancer victims to stay alive and stated:
"We try to buy a little more time. We try salvage radiation or surgery. We start a hormone blockade that leaves us as physical and chemical eunuchs.
"We lose the little sexual ability that we may have managed to cobble together and trade it for hot flashes, loss of muscle mass, loss of bone density, peripheral neuropathy, mood swings, and a host of other ailments.
"Despite the suffering that we endure, our cancer continues to march on. Now our only option to survive a little longer as it exists today is chemotherapy, where we have to introduce into our bodies chemicals that will hopefully kill the cancer, but will also kill us."
He acknowledged that Provenge will not cure his disease, but said, "it does offer an opportunity to extend my life."
Alvin Chin spoke on behalf of the Virginia Prostate Cancer Coalition and pointed out that Taxotere was approved when it extended life by only a couple months compared to a placebo. "Provenge extends life more than twice as long without the pain," he noted.
"The loss of hair, fingernails, vitality, your dignity is something you don't lose with Provenge," he pointed out.
Mr Chin told the panel that men will gladly trade the side effects of hormonal and chemotherapy treatments for the few and transient side effects of Provenge and gain more life in the process.
No one wants to die a hopeless and painful death, and worst of all no one gladly accepts chemotherapy, the only treatment available to men with hormone-resistant prostate cancer, he said.
He explained that the side effects of chemo are so bad that men refuse treatment because they want to have an improved quality-of-life in their final years. "By recommending approval you will give up to 50,000 waiting men, maybe more, new hope and new life with an alternative treatment that works," he said.
The customer base up for grabs in the prostate cancer industry is huge. According to the American Cancer Society, approximately 220,000 new cases of prostate cancer will be diagnosed in the US in this year alone and about 27,000 men face death from prostate cancer each year.
On March 29, 2007, after listening to all the presentations and testimony of cancer treatment advocates, in a unanimous vote, the committee determined that Provenge was safe, and that there was substantial evidence that the product works in treating late stage prostate cancer that no longer responds to hormone treatment by a 13-4 vote.
However, the meeting transcript reveals a calculated attempt by the conspirators to elicit the desired "no" response from committee on whether Provenge was effective, with a question that asked: "Does the submitted data establish the efficacy of Sipuleucel-T (APC-8015) in the intended population?"
This obvious stunt was quickly recognized by some panel members and the question was then rephrased to conform with the.law that requires the question to ask does the data submitted show "substantial evidence."
After the question was rephrased, the first expert to vote, Dr Richard Alexander, changed his "no" vote to "yes" and stated: "I mean the issue is -- yes, there is substantial evidence. I mean, the 150-some patients, they're substantial evidence."
Dr Jeffrey Chamberlain followed Dr Alexander and said: "I vote yes, there is substantial evidence."
And after him, Dr Larry Kwak said, "Yes, substantial evidence."
Dr Kurt Gunter voted yes and stated: "I do think it both meets the measure of substantial evidence, and I also believe that it's pretty definitive."
"And I think that these data," he stated, "even though they're complex, can be presented by oncologists to patients in a way that they can understand and make reasonable choices."
"So I definitely support that this is an effective therapy," he stated.
Once the question was changed, Dr Hussain stated, "to me "substantial" and "establish" are the same, and no to either. So no to both."
When Dr Woo was asked to vote, he stated in part: "Does it rise to the level of substantial evidence that it is effective? I don't think so, not even near."
The sudden change in the question seemed to throw Dr Scher off kilter and when the vote got to him he stated: "We have two questions. I would say yes to one, no to the second. The first question as posed, as established, I say no."
The panel chairman, Dr James Mule clarified that the question was "substantial evidence," and Dr Scher replied, "I will say no."
During the meeting, Dr Ke Liu, the FDA's clinical reviewer of the Provenge application, explained the advantage of using overall survival rates, as noted in the draft guidance document entitled, Clinical Trial Endpoints for the Approval of Cancer Drugs in Biologics. "Overall survival," he said, "is the most reliable cancer endpoints, usually the preferred endpoint, and the studies can be conducted to adequately to assess it."
"Demonstration of a statistical significant improvement in overall survival," he told the panel, "has supported new drug approvals."
Dr Liu also said an improvement in survival is a clinical benefit, and that the endpoint is precise and easy to measure because it can be documented by the date of death.
During the meeting, no doubt by accident, Dr Sher even acknowledged that "there's no argument that overall survial is a definitive endpoint, and that's what we're all seeking to achieve with our treatments."
However, on May 8, 2007, the FDA made history when for the first time, it denied the approval of a cancer drug despite the recommendations of its own advisory committee and despite the pleas from dying cancer victims during the advisory panel hearing.
By filing their lawsuit against FDA officials, the plaintiffs "seek to immediately enjoin the Defendants from denying, for even one more day, the distribution of Provenge to them."