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

Evelyn Pringle November 27, 2007

Dying prostate cancer patients waiting for the approval of Provenge, a new life-extending cancer vaccine, are being held hostage by an FDA infested with industry insiders with enormous financial interests in what has become a multibillion dollar cancer treatment racket for drug companies, cancer researchers, and treatment providers alike.

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 2 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.

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.

Three Lawmakers Give Terminal Cancer Patients Early Xmas Gift

Evelyn Pringle December 19, 2007

Three members of Congress recently sent a letter to the House Energy and Commerce Committee calling for a hearing to examine the conflicts of interest involved in the FDA’s decision to deny the approval of Provenge, a new life-extending vaccine for use with terminally ill prostate cancer patients who have no other treatment options.

In the December 13, 2007, letter to Rep John Dingell (D-MI), Chairman of the Committee, Congressmen Mike Michaud (D-Maine), Dan Burton (R-IN) and Tim Ryan (D-OH) said they had serious concerns about the FDA’s failure “to approve a potentially life-saving therapy for those suffering from advanced prostate cancer.”

“We need to ensure that the FDA gets life-saving drugs to the market as quickly and as safely as possible,” Rep Michaud said in a statement released to the media.

“Our priority is to ensure the prompt and efficient approval of therapies such as Provenge that could potentially benefit millions of Americans with cancer,” he stated.

Provenge belongs to a new class of immunotherapies that is designed to stimulate the body’s own immune system to attack cancer cells only, unlike chemotherapy, which attacks both cancer cells and healthy cells.

The new immunotherapies pose an imminent threat to the multi-billion dollar cancer research and treatment industry because if they turn out to be as effective as some experts predict, treatments involving radiation and chemotherapy for many diseases could become obsolete.

The FDA’s refusal to approve Provenge was extremely upsetting to members of the cancer community who have been closely tracking the approval of this vaccine since October 29, 2004, when the New York Times reported that Dendreon had announced that it had developed “an experimental vaccine extended the lives of men with advanced prostate cancer.”

This is supported by the results of a recent trial that reported 34% of the prostate cancer patients who received the vaccine were still alive after 36 months, compared to only 11% of the men who received a placebo.

On February 17, 2005, the Washington Post ran the headline: “Provenge: First Vaccine to Extend Lives for Advanced Prostate Cancer Patients”. The article quoted Jamie Bearse, of the National Prostate Cancer Coalition, as stating: “Whenever you have something that comes out that really kind of changes the treatment landscape in the prostate cancer field, it’s very encouraging.”

Chemotherapy with Taxotere, made by Sanofi-Aventis, is the only approved treatment for late stage prostate cancer patients. Treatment using this drug involves months of infusions and produces severe side effects. Provenge, on the other hand, is administered three times at 2-week intervals, and only one in four patients experiences side effects consisting of mild flu-like symptoms that last a day or two. Further, Provenge keeps working long after each infusion to help the body build up its immune system.

Experts estimate that between 300 and 600 patients a year die from the Taxotere treatment itself, and they say that no patients have died from treatment with Provenge.

The FDA’s Office of Cellular, Tissue and Gene Therapies Advisory Committee finally met to review the application for the approval of the vaccine. Specifically, the panel heard testimony from members of the prostate cancer community during an Advisory Committee hearing on March 29, 2007.

Cancer patients testified that the side effects of chemotherapy with Taxotere are so severe that many men refuse the treatment. Put simply, they do not want spend their last years of life living with the debilitating side effects.

They also pointed out that Taxotere was approved when it extended life by only a couple months and that Provenge extends life more than twice as long without the pain or loss of hair, fingernails, vitality, and, importantly, their dignity.

They told the panel that 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.”

At the end of the hearing, the panel voted 17-0 that Provenge was safe and 13-4 in favor of it having demonstrated substantial evidence of efficacy. This meant that the drug had met the burden of proof specified in the Food and Drug Administration Modernization Act of 1997, for immediate approval while Dendreon completed its ongoing study of the vaccine.

Under the FDA’s risk-benefit balancing test for drugs undertaken pursuant to 21 USC 355(d) as part of the premarket approval process, the FDA generally considers a drug safe when the expected therapeutic gain justifies the risk entailed by its use.

Applying that approach, FDA even has approved cancer treatments that are highly toxic and thus not safe as that term is ordinarily used, but that are, nonetheless, safe in the
relevant sense under the FDCA because the potential benefits to health outweigh the risks. (61 Fed Reg 44,413 (1996)).

Under this balancing test, the experts on the panel voted 17 to 0 that Provenge was safe, so there would be no reason to deny Provenge to cancer patients who are dying.

In determining whether or not the benefits outweigh risks, the FDA also is supposed to consider the availability of other drugs or treatments together with their safety profiles. In February 1996, the FDA Commissioner at the time, Dr David Kessler, testified before the Senate Committee on Labor and Human Recourses and told the panel, “FDA must determine if each new drug or device is safe enough in view of its anticipated benefits and the comparative benefit of other available treatments.”

In the case of Provenge, there are no other methods of treatments with comparative benefits to balance against the alternative of certain death.

In their request for a hearing, the lawmakers informed the Committee that a lawsuit has been filed by the Ohio-based nonprofit group, Care to Live, in federal court, accusing the FDA of ignoring conflict-of-interest issues with two advisers who were chosen to sit on the advisory committee that reviewed the application for the approval of Provenge.

The plaintiffs in the case include dying cancer victims, their family members, and doctors, who are suing collectively as members of Care To Live. The complaint alleges that “prostate cancer patients are living and dying in Ohio and families and doctors in Ohio want this treatment for their family, friends and patients.”

It also alleges that one doctor has 12 patients waiting for treatment and a John Doe plaintiff is one of several patients “who may die before he can receive Provenge.”

The defendants include FDA Commissioner, Dr Andrew von Eschenbach, Mike Leavitt, Secretary of the Department of Health and Human Services, Dr Richard Pazdur, the head of the FDA’s Office of Oncologic Drug Division, and Dr Howard Scher, chosen by Dr Pazdur to serve on the advisory panel to review the application for the approval of Provenge.

In their letter to the House Committee, the lawmakers ask for a hearing to discuss the FDA’s role in the Provenge decision and state, “there is reason to believe that serious ethics rules were violated by two FDA advisory panel members in their decision and that those violations played a role in the subsequent FDA decisions to not approve Provenge at this time.”

The letter points out that two of the negative votes on efficacy were made by academic oncologists Dr Maha Hussain of the University of Michigan and Dr Howard Scher of the Memorial Sloan-Kettering Cancer Center in New York.

They also note that Dr Scher is the lead investigator for a competing cancer drug made by Novacea and is listed as an adviser to a large venture capital firm that is (or was, at the time of the March 29. 2007, meeting) a major investor in Novacea; that firm is ProQuest Investments of Princeton, NJ.

“We believe the FDA should not be appointing scientists leading the testing of a rival drug for another firm onto an advisory committee evaluating Provenge nor should the FDA appoint an adviser to a large investor such as a competitive firm as a panel member,” the lawmakers state.

“Many ethical questions remain about the two panelists who voted no on approving this drug,” Rep Michaud said in a statement released to the media.

A Congressional hearing could mean big trouble for the officials involved in this escapade because as of December 1, 2007, investigations of potential criminal misconduct by FDA employees will be conducted solely by the Inspector General for the Department of Health and Human Services without any FDA involvement, according Senator Chuck Grassley, ranking member of the Senate Finance Committee, in a November 29, 2007 press release.

And that would include Dr Scher and Dr Hussain because members of advisory panels are considered “special government employees” of the FDA.

In September 6, 2007 letter, Inspector General David Levinson informed Commissioner von Eschenbach that he will now “independently investigate allegations concerning senior FDA officials and thereby eliminate any conflict of interest – in fact or appearance – created when FDA Office of Internal Affairs (OIA) agents are asked to investigate allegations of misconduct against a supervisory official.”

Mr Levinson specifically noted the increased congressional and media scrutiny over allegations of potential criminal violations of Federal conflict-of-interest statutes involving FDA and other officials that led to his office devoting increased attention and resources to ethics issues. “As a result,” he informed the Commissioner, “investigators and attorneys have developed significant expertise in handling these complex cases.”

Provenge will not doubt qualify as a “complex case” because in addition to being the lead investigator for Novacea’s clinical trials for Asentar, a treatment that would compete for treating the exact same patient population as Provenge, Dr Scher also is a member of the scientific advisory board for Novacea.

The lawmakers did not elaborate on Dr Hussain’s conflicts but she runs a close second to Dr Scher. She is an investigator for studies on treatments competing with Provenge and her husband owns stock valued at between $15,000 and $300,000 in three competing companies. She is also on an advisory board for Novacea and receives research funding from Sanofi-Aventis, according to faculty disclosures at the University of Michigan.

According to Care To Live, Dr Pazdur chose Dr Hussain and Dr Scher to serve on the panel so that they could persuade the other members to vote against approving Provenge.

However, when that mission failed, a follow-up plan was implemented in which Dr Hussain, Dr Scher and a Dr Thomas Fleming would send letters to the FDA, disparaging the vaccine and urging top officials to basically ignore the Advisory Committee panel’s recommended approval.

Under this plan, once the letters arrived, FDA officials would leak the letters to the media, specifically to, “The Cancer Letter,” which in turn would publish each one on the Internet roughly a week apart prior to May 15, 2007, when the FDA was required to announce a decision.

Care To Live now has discovered that the FDA not only leaked the letters to the press, but government officials actually had a hand in composing the letters. A document obtained through a FOIA request from the National Cancer Institute shows that Dr Scher’s letter had several authors, with the final copy submitted for his approval and signature.

One document, identified as “v3” (version 3) is titled, “FDA Letter Draft” and carries a date of April 3, 2007. The listed recipients are Andrew von Eschenbach, Janet Woodcock and Jessie Goodman.

This draft came from the computer of Dr Alison Martin at National Cancer Institute and shows 13 edits with embedded comments, most if not all of which were adopted or resolved by Dr Scher after he received comments from the other writers.

For instance, in one sentence, he inserted a comment that states: “I thought it might be a nice touch to quote their own guidelines – what do you think?”

Dr Scher is referring to his addition of the statement: “Scientific basis for the legal standard, FDA Guidance for Industry; Providing Clinical Evidence of Effectiveness for Human Drugs and Biological Products, May 1998.”

He also questioned the language used in a sentence that originally stated: “I am also the PI of the 10 Center Prostate Cancer Clinical Trials Consortium funded by the DOD focused on phase I and 2 trials in this disease.”

In the draft copy, Dr Scher inserts a question asking: “Is it really called “10 center…”? If not, I would call it Multicenter … no one uses the number of centers and I thought it was granting a mechanism eg P10.”

Another sentence in the draft states: “FDA doesn’t accept secondary endpoints unless primary endpoints are met – is there to be an exception here b/c it is OS? Should be no exceptions because of the complexities – then can name the e.g., heterogeneity, confounders, 2:1, whatever they are.”

At this point Dr Scher inserts the comment: “I change my input here – I see that the 2 trials were not confirmatory so don’t need to go down the path of secondary endpoints – the primary contradiction is inconsistent results.”

Dr Scher’s letter was clearly reviewed, edited, and partially authored by officials within the FDA and NCI. But how many people had access to the finalized version is unknown, making it impossible to determine for certain who leaked it to “The Cancer Letter” for publication on the Internet on April 13, 2007. In seeking a hearing, Care To Live is asking Congress to require FDA officials to answer that question once and for all.

According to Care To Live, the desperation evidenced by the efforts to block the approval of Provenge was the result of pressure from investors who had sold the stock short based on insider information that approval would be denied and thus, stood to lose millions if that tip turned out to be false.

A development that instantly raised suspicions came on May 31, 2007, when Novacea announced that it had entered into a partnership with Schering-Plough involving the research and development of its cancer drug Asentar, worth as much as half billion dollars.

Under this deal, Schering would fund the ongoing clinical trials of Asentar for which Dr Scher was the co-lead investigator. The news of the partnership resulted in an 86% increase in stock value for Novacea in one day.

All bets are on Dr Pazdur as the leaker due to his history of similar conduct a few years ago in the ImClone case, where he leaked the fact that the FDA was not going to review the application for the approval the cancer drug, Erbitux, and set off a firestorm of insider trading in December 2001.

Persons in the inner circle of ImClone immediately acted on the tip and sold off large amounts of stock and the company’s stock value plunged. The SEC began an investigation within days after the FDA’s decision was officially made public on December 28, 2001, and determined that Sam Waksal, one of the owners of ImClone, and his relatives sold over $10 million worth of stock in 48 hours on December 26 and December 27, 2001.

And of course, everybody knows the rest of the story. When the Waksal family started dumping stock, Sam Waksal’s broker, Peter Bacanovic, tipped off his famous client Martha Stewart and she quickly got rid her shares.

By January 9, 2002, less than two weeks after the insider trading ended, ImClone had lost nearly $1.5 billion in market value, according to the transcript of a June 9, 2002 Congressional hearing.

Dr Pazdur also used his buddies at the “The Cancer Letter” to make information public in the ImClone case.

It will be interesting to hear what Dr Pazdur has say if Congress holds a hearing on Provenge because the transcript from the ImClone hearing reveals that nobody ratted him out even though several members of Congress directly asked FDA officials, including Dr Pazdur, who leaked the information, and even though that hearing took place 6 months after the fact.

The transcript shows that when asked directly who leaked the information, they all talked in circles in order not to identify Dr Pazdur. For instance, Rep Ernie Fletcher put the question to the whole gang, stating: “Let me ask a question, and I guess this probably goes to Dr. Keegan, but if somebody else has a responsibility, don’t hesitate to answer it.”

“We got testimony earlier from Mr. Bryan Markison that on December 25, of all days, Christmas, that he received a call from someone, and I don’t know that we got that individual’s name. But he received a call on December 25 that you all were likely—well, not only likely, but that it was going to occur, that an RTF letter would be issued.”

He noted that the official letter that was sent was stamped on December 28, and asked flat out: “Who leaked the information, and is that normal to leak the information, or is that okay to leak the information?”

“It had tremendous impact on the executives, and family, friends, and other folks who ended up selling off a whole lot of stock based on that information,” he added.

The closest anyone came to identifying the leaker was when Ms Keegan said, Dr Pazdur says, “we do have the option, and in his Center, he will actually inform a sponsor, a commercial firm, that they would refuse to file the application ahead of issuing the letter.”

“There is no prohibition against telling a company that you will refuse to file their application,” she stated. “We did not choose to tell them that definitely before we sent the letter, but there is no prohibition against it.”

The main problem with this rambling answer is that ImCone’s application was not under review by Dr Pazdur’s “Center.” Ms Keegan office was in charge, and instead of talking in circles, the honest answer would have been for Ms Keegan to say that she did not exercise this so-called “option,” but that apparently, Dr Pazdur took it upon himself to exercise it for her.

Of course, that is assuming that she knew he was the leaker.