FDA’s Refusal to Approve New Cancer Vaccine – The Plot Thickens – Part II

Evelyn Pringle November 29, 2007

On November 26, 2007, CareToLive, the non-profit corporation that is suing FDA officials on behalf of terminal prostate cancer patients over the decision not to approve Provenge, a new life-extending prostate cancer vaccine, announced that a judge had dismissed the lawsuit.

The attorney for CareToLive, however, said an immediate appeal would be filed in the 6th Circuit Court in Ohio where the case will be heard by a 3-judge panel. “CareToLive will keep fighting to the Supreme Court if need be,” attorney Kerry Donahue says.

In its press release, CareToLive’s spokesperson, Melody Davis states: “Men are dying while a safe, effective treatment languishes outside of their grasp.”

The group also is vowing to put more pressure on lawmakers to investigate the Provenge debacle. “Congress needs to wake up and hold hearings immediately!” Ms Davis states.

“The evidence clearly shows our government violated these men’s right to live,” says Mike Kearney, a CareToLive board member.

“They can say it, explain it, and infer it any way they want, but the truth is they allowed over 16,000 men to die since May 8th without treatment while other men profited handsomely during their demise,” he states in the group’s press release.

Because the FDA refused to approve Provenge, prostate cancer patients and advocacy groups have organized public rallies in major cities, taken out a half-page ad in “The Washington Post”, placed ads on the sides of Washington, DC buses, and written thousands of letters and e-mails, lobbying Congress to hold hearings on the matter in an all-out effort to get the vaccine approved for dying prostate cancer patients.

“We are going to stand up for these men’s rights,” Attorney Donahue states in the press release.

Scott Riccio, founding member and lobbyist for another advocacy group, “A Right To Live,” who organized a rally at the FDA headquarters with CareToLive, also says his group will continue to focus on efforts aimed at Congress to hold public hearings.

A sign-on letter is available on the CareToLive web site at http://caretolive.com/ for people who want to join the effort to get Congress to investigate the FDA’s handling of Provenge.

Provenge is an active cellular immunotherapy designed to direct the body’s immune system to attack only cancer cells, in contrast to chemotherapy, which uses drugs to kill not only cancer cells but also other rapidly growing cells, while causing horrendous side effects.

Dendreon, a Seattle-based biotech company, makes Provenge. The only other treatment approved for late stage prostate cancer patients who would benefit from Provenge in more than 40 years, is the chemotherapy drug Taxotere (docetaxel) sold by Sanofi-Aventis.

A mere 3 injections of Provenge at 2 weeks intervals offers men with prostate cancer the chance to significantly prolong their lives without the negative effects that many months of chemotherapy can have on their quality of life.

On March 29, 2007, an FDA Advisory Committee (AC) reviewed Dendreon’s Biologics License Application (BLA) for Provenge. The AC’s 17 members voted to recommend immediate approval. Specifically, it voted 17-0 that the vaccine was safe and 13-4 that it demonstrated “substantial evidence” of efficacy, the Congressionally mandated standard.

In large part due to the fact that the FDA had never before refused to follow an AC panel’s recommendation to approve a cancer treatment for a patient population facing imminent death, doctors, patients, and the public at large believed that Provenge would be approved by May 15, 2007, and that a whole new era of immunotherapies for the treatment of many types of cancer would follow.

However, on May 9, 2007, the media reported that FDA Commissioner Andrew von Eschenbach had set a new precedent by refusing to approve Provenge for men with end-stage prostate cancer and issuing a Complete Response (CR) letter to Dendreon requesting more data that could take until 2010 to provide.

The CareToLive lawsuit alleges that Dr Richard Pazdur, director of the FDA’s Office of Oncology Drug, intentionally placed Dr Howard Scher, a researcher and oncologist at Memorial Sloan-Kettering Cancer Center, and Dr Maha Hussain, a researcher and professor at the Comprehensive Cancer Center, at the University of Michigan, on the Provenge AC panel in attempt to rig the votes against Provenge because he knew they stood to benefit significantly from a decision not to approve the vaccine.

Importantly, when they participated in the AC, both Dr Scher and Dr Hussain were acting as special government employees, positions that requires an additional moral and ethical duty on their part in the eyes of the public.

After failing to sabotage Provenge during the public hearing, Dr Scher and Dr Hussain wrote letters to the FDA, filled with misinformation to improperly lobby FDA decision-makers and place public pressure on them to withhold approval of Provenge.

Adding to the conspiratorial atmosphere surrounding the two letters, as well as a similar letter sent to the FDA by Dr Thomas Fleming, is the fact that all three letters were leaked for publication on the internet to “The Cancer Letter”, a non-peer-reviewed industry newsletter, with obvious calculated release dates of 1-week apart.

The significance of leaking insider FDA information to the public on whether or not a drug will be approved cannot be over-stated. FDA officials and advisory panel members have the ability to effect billions of dollars in profits and stock value.

CareToLive and other advocacy groups are demanding an investigation to determine who at the FDA leaked the letters to the media. Sources familiar with the case say the likely culprit is Dr Pazdur as he was the FDA official responsible for leaking insider trading information in the ImClone cancer drug case that landed Martha Stewart in prison for 5 months after she sold off her stock based on a tip that originated with Dr Pazdur and then lied to the Feds about her reasons for doing so.

Acting on Dr Pazdur’s tip, in telling family members and friends to dump their stock in the days before the official FDA decision was released, also earned Sam Waksal, the co-founder of ImClone, a 7 year prison sentence.

According to CareToLive, it’s “inconceivable” to argue that it could be a coincidence that Dr Pazdur picked two doctors who would both personally benefit from the non-approval of Provenge, who both acted as expected at the hearing considering their conflicts of interest, and then wrote similar letters to the FDA that were leaked to the same publication.

Never in the history of the FDA have two expert panel members with extreme conflicts of interest worked in conspiracy with one another to attack a product after the public hearing was over, according to a November 9, 2007 brief filed by CareToLive.

On May 29, 2007, just three weeks after Dendreon received the CR letter from the FDA, the competing cancer drug company Novacea announced a funding deal with Schering-Plough worth close to a half a billion dollars in which Schering agreed to jointly fund and develop clinical trials for the cancer drug Asentar combined with Sanofi’s Taxotere.

The day the news was released, Novacea’s stock value rose 86%.

Shortly after the announcement of the Novacea-Schering deal, it became known that Dr Scher was a lead investigator for the clinical trials financed by Novacea and Schering on treatments with Taxotere and Asentar, in direct competition for the same prostate cancer patients that would benefit from Provenge.

On July 26, 2007, Rory Kearney, President of CareToLive, filed a Citizen’s Petition with the FDA to request reconsideration of the agency’s failure to approve Provenge and pointed out that Dr Scher had cashed in on Wall Street “when the competing company he works for received $440 million.”

“That deal” the Petition states, “would not have happened if Provenge had properly been approved.”

Reports that Dr Hussain serves as a consultant and advisory board member to Novacea also emerged soon after the Schering deal was announced.

In the company’s press release, Novacea reported that the ongoing Asentar Phase 3 trial was on track and the firm expected to complete enrollment by the end of the year. The approval of Provenge would have caused major complications for the enrollment of prostate cancer patients and if Provenge were to become the new “standard of care”, it would represent an imminent threat to the cancer research industry as a whole.

For successful enrollment in clinical trials, researchers need a steady flow of patients with specific types of cancer and the competition to find these patients is fierce.

It’s especially difficult to enroll patients who are facing death because a trial may be testing a new treatment against a placebo, which means trial participants have to be told up front that they might not receive any treatment.

And even when enrollment is successful, many trials last years, and there is always the threat of patient dropout if side effects occur or if a promising new treatment such as Provenge becomes available.

For the most part, the current trials for late-stage prostate cancer involve chemotherapy and many terminally ill men do not want to spend their last days experiencing the horrible side effects associated with chemo.

The lengthily trail of conflicts of interest that lead to the gang who succeeded in stopping the approval of Provenge is easy to track on the internet. The top recipients of cancer research funding in the US include Dr Pazdur’s previous employer of 11 years, the MD Anderson Cancer Center at the University of Texas, along with Dr Scher’s employer, the Memorial Sloan-Kettering Cancer Center, and Dr Hussain’s Cancer Center at the University of Michigan.

Prior to his appointment as leader of the National Cancer Institute in 2001, the current FDA Commissioner, Dr von Eschenbach, was executive vice president and director of prostate cancer research at the MD Anderson Cancer Center.

Before Dr Pazdur and Dr von Eschenbach left MD Anderson, Dr John Mendelsohn was their boss as President of the Center Dr Mendelsohn in fact, is said to be the guy who recommended Dr von Eschenbach to Bush for the top position at the National Cancer Institute.

At the same time, Dr Mendelsohn was also a member of ImClone’s board of directors and a board member at Enron, another infamous firm that was busted for insider trading around the same time as ImClone.

Congress held hearings on the ImClone debacle in June and October of 2002, and during testimony, it came out that Dr Mendelsohn had made over $6 million in 2001 by selling ImClone stock without informing cancer patients enrolled in clinical trials at MD Anderson that he was a major stockholder in the company that would benefit from the trials.

When lawmakers tried to question him about the Enron fiasco, Dr Mendelsohn said he was there to talk about ImClone not Enron.

Dr Scher, Sloan Kettering and MD Anderson also benefit financially from the Prostate Cancer Foundation. According to the group’s Federal Tax Form 990 for 2006, Sloan Kettering and MD Anderson received the largest share of money awarded in 2004, 2005, and 2006. The Foundation’s 2005 Annual Report shows their total grants through 2005 equaled about $33 million, far surpassing funding to any other research centers.

Dr Scher serves on the panel that decides who will receive research grants and funding.

The Foundation was founded in 1993, by junk bond king Michael Milken, who served time in prison for securities fraud. The individual who helped Mr Milken establish the Foundation is Dr von Eschenbach, according to the transcript of a September 22, 2004 web conference posted on WebMd.

At the time of the web conference, Mr Milken reported that since 1993, the Foundation has helped fund 1100 research studies in dozens of clinical trials. Dr Hussain is a Consortium Clinical Investigator, according to the group’s 2005 Annual Report.

The Prostate Cancer Research Program is the leading source of government funding for prostate cancer research in the US. Since 1997, a total of $730 million has been appropriated for the Program, including $80 million in 2006.

The Program awards research and training funding, and one such grant, the Clinical Consortium Award, supports the creation of a major multi-institutional clinical trial resource and Dr Scher leads this multi-institutional consortium. The participating clinical sites and lead investigators include none other than Dr Hussain and the University of Michigan Comprehensive Cancer Center, according the Program’s government reports.

Less than a month before the Provenge AC panel held the public hearing, on February 26, 2007, Ed Susman reported in MedPage Today, that Taxotere-based combination therapy was being investigated in a dozen trials, quoting investigators who said there were four phase III Taxotere-based combination trials and eight phase I and II trials.

Mr Susman also noted that in a symposium titled, “Improving Upon Current Standards: The Integration of Novel Therapies in the Treatment of Androgen-Independent Prostate Cancer,” sponsored by Novacea, Dr Scher described a number of the trials.

At the end of the article, MedPage lists Dr Scher as reporting only that he receives grants and research support from Novartis, Novacea, Bristol-Myers Squibb and Sanofi-Aventis, which minimizes the fact that he is involved in most of the clinical trials discussed.

Dr Scher also benefits from financial interests in ProQuest Investments. The firm’s main focus is on prostate cancer therapies and since 2003, ProQuest has invested heavily in Novacea. Dr Scher sits on the firm’s Board of Directors, and is a member of its scientific advisory board.

In addition to being a consultant and advisory board member of Novacea, Dr Hussain’s Michigan University faculty disclosures list her as receiving research funding from Sanofi-Aventis. The University’s 2005-2006 Annual Report says she is a clinical investigator “with a particular focus on prostate and bladder cancer” and “serves as principal investigator of three national NCI-sponsored phase II and phase III clinical trials.”

Under disclosures for program faculty listed in October 2006, for a CME seminar titled, “Prostate Cancer: Beyond First Line Hormones,” Dr Hussain reported financial relationships to include serving on an advisory board and as a consultant to Novacea and receiving research funding from Sanofi-Aventis.

Dr Hussain’s disclosures related to serving on the advisory panel show her husband owns stock valued at $15,000-$300,000 in three companies that compete with Provenge.

And for what its worth, a web site sponsored by the Huffington Post on campaign contributions shows that during the 2004 Presidential election cycle, Dr Hussain, who received her medical education in Bagdad, Iraq, gave George W Bush $2,000. Her husband also gave Mr Bush $2,000, and Sal Jafar, described as a self-employed physician and listed at the same address, gave the Republican National Committee $2,050.

In his letter that was leaked to the press, Dr Scher spelled out the threat that Provenge posed to the cancer research industry when he noted that the FDA’s approval would provide the endorsement of the vaccine as the “standard of care” and raise it “to a position of being the new ‘control’ arm for future randomized phase 3 trials that are being designed for the regulatory approval of any new experimental agent or approach.”

So, in layman’s terms, if Provenge became the new “standard of care,” any new therapy for late stage prostate cancer may need to be tested against Provenge for FDA approval.

On November 5, 2007, definite signs indicating that one of the main sources of income for Dr Scher and Dr Hussain might soon run dry appeared in the media after Novacea announced that the company had ended its Phase 3 clinical trial of Asentar after the Data Safety Monitoring Board found a higher death rate in patients who received Asentar.

The study was comparing the benefits for late stage prostate cancer patients of weekly chemotherapy with Asentar plus Taxotere against the current standard of care of Taxotere alone. To date, more than 900 of the planned 1,200 patients were enrolled in this study at multiple centers in countries that including the US, Canada, Germany, and Central Europe.

According to Novecea’s November 12, 2007 SEC filing, the company has “ended and suspended enrollment in clinical trials for our lead product candidate, Asentar�, and we cannot give any assurance that it will receive regulatory approval or be successfully developed or commercialized.”

Under the section titled, “Risks Related to Our Business,” the company points out that the firm has never shown profits and possibly never will now. “We have incurred losses since inception and anticipate that we will continue to incur losses for the foreseeable future. We may never achieve or sustain profitability,” it states.

Had Provenge been approved, the entire chemotherapy research industry that has proven to be so profitable for so many entities over the past 2 decades may have collapsed like a house of cards.

And the same goes for the chemo cartel because infusions of chemotherapy drugs represent the primary source of income for most oncologists. In 2005, cancer doctors billed about $4.4 billion for chemotherapy and drugs used to treat anemia caused by chemotherapy, with Medicare covering 80% of the bill, according to a report by Alex Berenson in the June 12, 2007, “New York Times”.

If the FDA had approved Provenge and word got out that a new 3-infusion vaccine was available that extended survival far longer than chemo with minimal side effects, no prostate cancer patients would have been willing to spend the little time they had left battling the grueling side effects of months of chemotherapy.

Clearly, Provenge would have been the treatment of choice, had the FDA allowed these dying men a choice.

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