Evelyn Pringle October 1, 2007
A lawsuit recently filed in a federal court in Ohio against FDA officials on behalf of terminal cancer patients provides a rare window into the inner workings of an agency hijacked by pharmaceutical industry giants and stacked with insiders by President George Bush to guard against any threat to the profits of his top campaign contributors.
The lawsuit's complaint describes a conspiracy orchestrated by top FDA officials to basically drive a small company, Dendreon, out of business with the obvious goal of eliminating competition in what has become a thriving new industry involving the treatment of men with prostate cancer.
The complaint gives the details of a step-by-step plot to sabotage the FDA approval process of Provenge, the first-of-a-kind vaccine that can prolong the lives of men with late-stage cancer.
Prostate cancer patients have been waiting for the approval of Provenge for years. The New York Times first reported on a study back on October 29, 2004, the day after Dendreon announced the results that showed that "an experimental vaccine extended the lives of men with advanced prostate cancer."
The findings also were discussed by Dr Eric Small of the University of California at San Francisco in February 2005, at a meeting in Florida that was co-sponsored by the American Society of Clinical Oncology. Here, he presented the study in which Provenge was given to a group of 82 men whose cancer had progressed after surgery and radiation treatment, and a similar group of 45 men who had received a placebo.
After 36 months, the study showed that 34% of the men who received Provenge were still alive compared to only 11% of the group who received a placebo, or a 23% difference.
On February 17, 2005, the Times reported that the 4.5-month increase in survival that was achieved by Provenge is greater than the roughly 2.5-month benefit shown in clinical trials of Taxotere, a drug from Sanofi-Aventis.
"Taxotere is the only approved chemotherapy for patients, like those in the Provenge trial, whose cancer has spread beyond the prostate gland and is no longer being controlled by hormonal therapy," the article said.
Dr Small told the Times that Provenge improved survival for all patients, not just those with less aggressive cancers, and said "the treatment was much less toxic than chemotherapy, with the main side effects being flu-like symptoms that last a short time."
The list of plaintiffs in the lawsuit, first and foremost, includes dying cancer victims, along with their family members and doctors, who are collectively suing as members of a non-profit corporation called CareToLive (CTL).
The plaintiffs allege 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."
According to the complaint, one doctor has 12 patients waiting for treatment and a John Doe plaintiff "is one of several Ohio prostate cancer patients who may die before he can receive Provenge."
The named defendants in the case include the current FDA Commissioner, Dr Andrew von Eschenbach, and Mike Leavitt, in his supervisory capacity over the FDA as Secretary of the US Department of Health and Human Services.
And let it be noted that the lead defendant, Dr von Eschenbach, became the FDA Commissioner following a two-month stint by Dr Lester Crawford, only because Lester was booted out of office and found guilty of charges that he failed to disclose his own financial ties to companies regulated by the FDA.
The two other named defendants in the CTL lawsuit are 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 convened to consider the approval of Provenge.
According to the complaint, Dr Pazdur "intentionally violated Federal Regulations" by improperly controlling the make up of the advisory committee and by "applying improper pressure" on panel members and other FDA employees "in an effort to achieve a predetermined outcome of his choosing."
The plaintiffs allege that when Dr Scher was chosen to serve on the panel, he failed to disclose all conflicts of interest and his own personal interests in urging a decision that Provenge not be approved for men dying of cancer and that Dr Scher acted in "a manner that has callously deprived cancer patients access to a safe and effective immunotherapy."
It also should be noted that the legal filings show one lone attorney, Kerry Donahue, of the Dublin, Ohio Bellinger & Donahue law firm, up against a "dream team" of attorneys with unlimited access to tax dollars and the full force of the federal government, which includes US Attorney Gregory Lockhart, Assistant US Attorneys Mark D'Alessandro and John Stark, the Director of the Office of Consumer Litigation, Eugene M. Thirolf, along with Andrew Clarke and Daniel Crane-Hirsch, Trial Attorneys from the Office of Consumer Litigation in the US Department of Justice.
According to the lawsuit, the FDA indicated that there were sufficient data submitted from the clinical trials of Provenge to immediately evaluate the product, so Dendreon filed a Biologics License Application in December 2006, which was granted fast track approval designation in January 2007, establishing May 15, 2007 as the date for an FDA decision.
Congress established the fast track approval program to expedite the approval of drugs for terminally ill patients.
In a blatant attempt to corrupt the Provenge advisory panel, Dr Scher was granted a waiver even though he is the chief of genitourinary oncology services of the Center for Prostate Cancer, at the Memorial Sloan-Kettering Cancer Center and the Center has a received a grant for a study from a competing company valued at $100,000-$300,000 and he owns stock valued at between $5,000 and $100,000 in a company that competes with Dendreon.
He also serves as an advisory board member to the venture capital fund ProQuest Investments LP. A 1998 document, entitled "The Opportunity in Cancer: Goldberg's Variation" says "Prostate cancer will be the focus of the ProQuest Investment LP, a new venture fund founded by Jeremy Goldberg", and "ProQuest raised $40.5 million in its first closing."
Dr Scher also is listed on some documents as an officer and member of the board of directors of ProQuest.
However, a later May 2000 document discusses the "Start-Up" issue and says, "ProQuest Investments is a $100 million oncology-focused investment fund, partnered by Jeremy Goldberg and Jay Moorin."
Under "Companies", the report lists Dr Scher's "Memorial Sloan-Kettering Cancer Center", among many others, but Dendreon is not one of them.
According to May 15, 2006, SEC filings, ProQuest and its principals have a major stake in Novacea. For instance, at the time of the filing, ProQuest Investments II, LP held 1,779,767 shares, ProQuest Investments II Advisors Fund, LP was listed with 75,508 shares, ProQuest Associates II LLC held 1,855,275 shares, and Jay Moorin was listed with 1,910,988 shares.
Dr Scher also is on a scientific advisory board for Novacea and is the co-lead investigator of the company's Asentar Phase III clinical trial of patients in the same stage of prostate cancer as patients who would be treated with Provenge.
Another conflicted panel member chosen by Dr Pazdur, Dr Maha Hussain, a professor at the University of Michigan, was granted a waiver even though she is the principle investigator for a study funded by a competing company and her husband owns stock valued at between $15,000 and $300,000 in three competing companies.
Under Faculty Disclosure Declarations, Dr Hussain is listed as being a consultant to, and an advisory board member of, Novacea and receiving research funding from Sanofi-Aventis, the maker of the chemotherapy drug Taxotere, the only product on the market FDA approved for the treatment of the cancer patients who would benefit from the approval of Provenge.
Dr Scher is also the lead investigator on a clinical trial investigating Taxotere in treating early-stage prostate cancer - a trial that some experts say would be adversely affected by the approval of Provenge.
Another conflicted member, Dr Savio Lau-Ching Woo, a professor of gene and cell medicine at Mount Sinai School of Medicine, was granted a waiver even though an affected company has patented a gene therapy technology that he invented which is being studied in prostate and other cancers and in the last 12 months Dr Woo has received an amount less than $15,000 from the patent.
Although in the end, the industry plants failed to corrupt the decision of the advisory panel, because the committee said Provenge was safe and that the data submitted show "substantial evidence" of efficacy, the efforts to derail its approval continued and on May 8, 2007, the FDA refused to approve the vaccine.
Instead of approval, the agency issued a Complete Response letter that required Dendreon to provide additional data that could take up to 2 years to accumulate. During that time, as many as 60,000 men will die from prostate cancer - many of whom could have benefited from Provenge.
The most blatant evidence of the conspiracy alleged in the lawsuit emerged in a May 30, 2007 press release, when Novacea and industry giant Schering-Plough announced that they had entered into an exclusive worldwide license agreement for the development and commercialization of Asentar and noted that Novacea was currently conducting a large international Phase 3 trial evaluating Asentar in 900 patients with androgen-independent prostate cancer.
Under the terms of the agreement, all total Novacea will receive close to a half a billion dollars.
Showing posts with label Schering-Plough. Show all posts
Showing posts with label Schering-Plough. Show all posts
Tuesday, August 3, 2010
FDA Industry Insiders Derail Approval of New Cancer Treatments
Evelyn Pringle October 10, 2007
George W Bush's FDA, stacked with insiders from the industry that literally carried him to Washington, has stooped to a new low to protect the obscene profits of the multi-billion dollar cancer industry by blocking the approval of a new class of immunotherapies that can extend the lives of dying cancer patients with minimal side effects.
In the May 14, 2007, Wall Street Journal, a former medical officer in the FDA Office of Oncology Products, Dr Mark Thornton, denounced the FDA's decisions, and stated, "May 9, 2007, should be cited in the annals of cancer immunotherapy as Black Wednesday."
"Within an eight-hour period that day," he wrote, "the FDA succeeded in killing not one but two safe, promising therapies designed and developed to act by stimulating a patient's immune system against cancer."
Experts say, the new immunotherapies hold promise for many forms of cancer. "FDA's hubris will affect the lives and possibly the life spans of cancer patients from nearly every demographic, from elderly men with prostate cancer to young children with the rarest of bone cancers," according to Dr Thornton.
With the approval of the new therapies, the profits, along with the horrendous side effects of the only treatments now available, could become a thing of the past. "One day current treatment approaches such as surgery, radiation and chemotherapy, which often kill most but not all of a cancer, could be made obsolete by a potent immune response that eradicates the cancer cells and provides subsequent protection against return and relapse," Dr Thornton wrote.
As such, the new therapies pose a grave threat to the cancer industry as a whole, and the lost profits would not be limited to the sale of products. The pharmaceutical giants have spent a small fortune to gain control of every segment of the industry, from researchers to government regulators, and every year, billions of dollars flow through a nationwide network of research institutions and treatment providers under the guise of finding a cure for cancer.
However, the profits up for grabs have become so enormous that critics say the goal of industry-controlled research is no longer focused on finding a cure for cancer to save lives. Instead, the focus is on thwarting the development and approval of new therapies in order to protect the profits of the treatments already on the market.
The FDA's refusal to approve Provenge, a new immunotherapy vaccine manufactured by the Dendreon Corporation, has caused major outrage in the cancer community. Provenge supporters have sent thousands upon thousands of letters and other correspondence to the FDA, members of Congress, the Department of Justice and others.
In addition, the Ohio-based non-profit corporation, CareToLive, has filed a lawsuit on behalf of terminal cancer patients seeking a declaratory judgment that the FDA acted "arbitrarily" and "capriciously" by denying patients access to Provenge, in violation of their constitutional right to live.
Dendreon sought approval to treat late-stage androgen-independent prostate cancer (AIPC) patients who have no other options. A study presented to an FDA Advisory Committee at a March 29, 2007, meeting showed that, after 36 months, 34% of the men who received Provenge in a clinical trial were still alive, compared to only 11% of those who received a placebo.
Provenge is designed to stimulate the patient's own immune system to specifically attack only cancer cells, unlike chemo drugs that attack any fast-growing line of cells.
Patients who qualify for Provenge have already had their prostates removed or have undergone radiation and hormone therapy. Eligible patients receive a one-time round of treatment consisting of 3 visits to a urologist's or oncologist's office to give blood, and 3 visits for the blood enhanced with Provenge to be infused back into the body.
On September 10, 2007, CareToLive filed a motion asking the court to issue an order enjoining the FDA from denying the marketing and distribution of Provenge. The plaintiffs charge that within six months, another 15,000 patients will have died waiting for justice.
The memorandum filed with the motion points out that the only available treatment approved for terminal AIPC in the last 42 years is a chemo drug, Taxotere. "The effectiveness of Taxotere," it states, "is so superficial, and the side effects so severe, that most men decline the treatment, as the risks far outweigh the benefits."
According to the filing, between 300 and 600 patients per year die from the Taxotere treatment itself. "This is truly amazing," the memo states, "considering the cost of the treatment and the cost of hospitalization and that the average benefit is an increase in survival of only 2 ½ months."
In contrast, the Provenge safety profile is so good that nobody has died from it and less than one in four patients experience side effects consisting of mild flu-like symptoms lasting one or two days, the memo notes.
The defendants named in the lawsuit include Mike Leavitt, Secretary of the US Department of Health and Human Services; FDA Commissioner Andrew von Eschenbach; Dr Richard Pazdur, head of the FDA's Office of Oncologic Drug Division, and Dr Howard Scher, chosen by Dr Pazdur to serve on the advisory panel set up to review the approval of Provenge.
CareToLive is represented pro bono by Attorney Kerry Donahue, of the Dublin, Ohio law firm Bellinger & Donahue, while the FDA officials are represented by a legal team of 11 government attorneys, at last count, funded by tax dollars.
The plaintiffs allege that the defendants engaged in a conspiracy to prevent the approval of Provenge and that Dr Pazdur, "purposely located two conflicted oncologists who he was sure for a variety of reasons would be anti-Provenge and he instructed them to try to derail the approval of Provenge."
The plaintiffs charge that, by choosing Dr Scher, and also Dr Maha Hussain, to serve on the advisory panel, Dr Pazdur "likely found two of the most conflicted oncologists in the country to sit in judgment of Provenge, and who would both assuredly continue his plot to lobby others at the FDA to vote for non-approval."
At the behest of Dr Pazdur, and for their own future political and monetary gain, the plaintiffs claim, "these two oncologists did everything they could think of to obstruct and impede the approval of Provenge."
The waiver of conflicts of interest granted by the FDA to Dr Hussain, which allowed her sit on the panel, reveals that she is the lead investigator on a research contract awarded by a company that competes with Dendreon, and her husband owns stock in three competing companies valued at between $15,000 and $300,000.
The lawsuit alleges that, as part of the conspiracy, on May 9, 2007, the FDA denied terminally-ill patients access to Provenge, even though the FDA Advisory Committee recommended approval, found the vaccine safe by a 17-0 vote and found there was "substantial evidence" of efficacy with Provenge by a 13-4 vote.
In an attempt to derail an approval recommendation by the panel, the plaintiffs claim that, prior to the vote on efficacy, Dr Pazdur and "his co-conspirators changed the statutory question regarding efficacy from 'substantial evidence' to 'absolute certainty' of efficacy, in an effort to obtain a 'no' vote on Provenge."
However, during the voting, this manipulation was discovered and promptly corrected by the FDA's Dr Celia Witten and Dr Jesse Goodman, and by an overwhelming majority, the panel voted "yes" to the revised efficacy question.
"It is unprecedented for the FDA to overturn the Advisory Committee on such a positive vote when men are out of options, delaying approval and asking for more trials," according to CareToLive spokesman Mike Kearny in an August 2, 2007, press release.
"Men are dying now," he states. "They do not have years to wait."
In the case of Provenge's approval, the profits at stake could not be higher. Prostate cancer is the most common non-skin cancer in the US and the third most common cancer worldwide. More than one million men in the US have prostate cancer, with an estimated 232,000 new cases diagnosed each year and more than 30,000 men face death from the disease each year.
As an initial treatment, when diagnosed with prostate cancer, most men have their prostate removed, or undergo radiation, which can lead to various degrees of incontinence and impotence. After the initial treatments fails, hormone therapy is given to block the production of androgens such as testosterone, needed for cancer cells to grow, and some men undergo testicle removal in an attempt to stop the androgens from spreading the cancer.
With AIPC patients, prostate cancer has usually gone into remission and then returned, spreading to other parts of the body including the bones, lymph nodes, bladder, rectum, liver and lungs. All men who do not die of other causes progress to the final stage where the cells no longer respond to hormone therapy. Provenge is intended for use by patients who have already failed other types of therapy.
Because Taxotere is the only approved drug, Sanofi would have suffered the greatest immediate loss had Provenge been approved. According to firm's 2006 Annual Report, Taxotere was the company's 4th best-selling product in 2006, and the US is listed as the number one country contributing to sales.
As far as profits per dose, in the February 7, 2007, article, "What Does It Cost to Have Cancer?", a patient who received the chemo drug for breast cancer in 2006 reported that "each infusion of Taxotere cost over $16,000."
She also stated: "That's just for the drug, not administration or anything."
According to the lawsuit, defendant Dr Scher, Chief Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, is a scientific advisor and lead trial investigator for a competitor of Dendreon called Novacea. Under faculty disclosures at the University of Michigan, Dr Hussain is listed as an advisory board member of Novacea, and she receives research funding from Sanofi.
Dr Scher also has an interest in ProQuest Investments, which stood to reap windfall profits if Provenge was not approved. ProQuest is a venture capital fund established in 1998, in large part by Michael Milken, who was given the nickname "Junk Bond King," after being indicted on nearly 100 counts of insider trading and sentenced to 10 years in prison, in addition to being barred from the securities industry for life.
The ProQuest fund was established with a specific focus on prostate cancer, and SEC filings show that ProQuest and its principals are major shareholders of Novacea.
Citing documents from ProQuest, the plaintiffs allege that Dr Scher is a "ProQuest Executive" and "member of the Board of Directors", ProQuest reaps millions of dollars investing in prostate cancer companies based on advice from doctors such as Dr Scher, and ProQuest own stock in direct competitors including Novacea.
Dr Scher receives compensation from ProQuest as a scientific advisor recommending investments and for conducting clinical trials that result from the investments. He also holds an ownership interest in ProQuest.
The lawsuit also alleges that Dr Scher receives research support from the Prostate Cancer Foundation, as well as financial benefits, as one of a consortium of members who reviews new research on cancer drugs to determine which grants should be awarded by the Foundation.
The PCF, also founded by Mr Milken, is one of the largest sources of funding for the National Cancer Institute and government research programs. A following of the tangled web involved in the PCF reveals that Dr Jonathan Simons, President of the Foundation, Dr Stuart Holden, Medical Director, and Dr Howard Soule, an Executive Vice President of the Foundation, are all scientific advisors to ProQuest.
Another research arm found to be infested with several of the same insiders is the Prostrate Cancer Research Program, within the Department of Defense, which since 1997 has been appropriated a total of $730 million by Congress. According to a PCRP report, "Today, the PCRP is the second leading source of extramural prostate cancer research funding in the United States."
The PCRP funds a Clinical Consortium Award to support the creation of a major multi-institutional clinical trial resource, "to speed development of novel therapeutics that will ultimately decrease the impact of the disease."
Here, too, Dr Scher is listed as the leader of the consortium, and the list of participating clinical sites and lead investigators includes none other than Dr Hussain. Dr Simons is listed as developing new clinical therapeutics for late-stage prostate cancer, but a review of upcoming research listed in the report shows immunotherapies are not in the cards.
These consortium members are invaluable to the industry and investors due to their unique access to insider information about clinical trials and influence over the FDA approval process. Evidence of this claim came on May 30, 2007, less than 3 weeks after approval for Provenge was denied, when Novacea announced an agreement with Schering-Plough worth over $450 million, in which Schering agreed to jointly fund and develop Asentar, a competing prostate cancer drug, for which Dr Scher happens to be the lead investigator.
"The partnership leverages Novacea's existing capabilities with Schering-Plough's experienced development, regulatory and commercial teams and will provide Novacea with an opportunity to support the commercialization of Asentar in the United States," John Walker, company chairman and interim CEO, stated in a May 30, 2007 press release.
A May 2000 ProQuest document provides insight about the investment firm's interest in Asentar's success and states: "ProQuest Investments is a $100 million oncology-focused investment fund, partnered by Jeremy Goldberg and Jay Moorin."
Mr Moorin owned 1,910,988 shares of Novacea stock at the time of a May 15, 2006, SEC filing, and the ProQuest document mentions an investment from Domain Associates, "whose general partner, Jim Blair, has also worked with the fund to plot its strategy."
As it turns out, Mr Blair and Mr Moorin were both members of Novacea's board of directors when the Schering deal was set up. However, apparently their services are no longer needed, because on August 30, 2007, Novacea announced the resignation of James Blair and Jay Moorin, effective September 4, 2007, and September 19, 2007, respectively.
All that said, it does not take a financial genius to figure out that this whole deal could have gone up in smoke had Provenge been approved, because there would have been a drastic drop in the enrollment of late-stage cancer patients in clinical trials as soon as they learned that there was a new vaccine that could not only increase their survival rate but allow them to live out their final days without the agonizing side effects of chemotherapy.
Provenge's approval also would have caused many patients currently participating in trials to drop out. Novacea's 2006 Annual Report filed on April 2, 2007, less than 2 months before the Shering announcement, warned that the "clinical development and regulatory approval processes inherently contain significant risks and uncertainties."
The report shows Novacea was going broke trying to keep the Asentar trials running, with research and development expenses associated with the drug of $12.9 million for the year ended December 31, 2006, up from $7.3 million for the year ended December 31, 2005.
The $5.6 million increase was due primarily to the Phase 3 Asentar trial, and the filing warns that Novacea could experience many delays in getting its product to market due to problems in trials including, "patient enrollment may be slower than expected at trial sites due to factors including the limited number of, and substantial competition for, suitable patients with the particular types of cancer required for enrollment in our clinical trials".
It also notes that there "is a limited number of, and substantial competition for, suitable sites to conduct our clinical trials; clinical trial sites may terminate our clinical trials"; "patients and medical investigators may be unwilling or unable to follow our clinical trial protocols;" and "patients may fail to complete our clinical trials once enrolled."
In addition, another ongoing trial is evaluating Asentar as part of a combination therapy for AIPC patients with Sanofi's Taxotere. If safety or efficacy issues arise with Taxotere, the annual report warns, Novacea could experience significant regulatory delays, and the clinical trial may need to be terminated or redesigned.
Even if Asentar were to receive FDA approval, Novacea would continue to be subject to the risks that could arise with Taxotere or that Taxotere may be replaced as the standard of care for AIPC. "This could result in Asentar ™ being removed from the market or being less commercially successful," the report states.
Ironically, in one of 3 derogatory letters sent to the FDA urging the non-approval of Provenge leaked to the media following the failed efforts to rig the advisory panel vote, Dr Scher discussed the same fatal effects that the approval could have on the research industry. "An approval recommendation has far reaching implications beyond making the product available that the data simply do not support or justify," he wrote.
Approval would provide the Agency's endorsement of Provenge as a "standard of care" for men with AICP, he said, and by extension, elevate Provenge "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."
In other words, all the billions of dollars invested in the clinical trials now underway, or set to begin, conducted in hopes of gaining FDA approval for a new ACIP treatment, could go right down the drain if Provenge is approved as the first-line treatment for this patient population.
Dr Scher is probably more aware of this fact than anybody. On February 26, 2007, MedPage Today reported that in a satellite symposium titled, "Improving Upon Current Standards: The Integration of Novel Therapies in the Treatment of Androgen-Independent Prostate Cancer," sponsored by Novacea, Dr Scher said Taxotere-based combination therapy is being investigated in a dozen clinical trials for ACIP patients, and he reported receiving grants and research support from both Novacea and Sanofi.
George W Bush's FDA, stacked with insiders from the industry that literally carried him to Washington, has stooped to a new low to protect the obscene profits of the multi-billion dollar cancer industry by blocking the approval of a new class of immunotherapies that can extend the lives of dying cancer patients with minimal side effects.
In the May 14, 2007, Wall Street Journal, a former medical officer in the FDA Office of Oncology Products, Dr Mark Thornton, denounced the FDA's decisions, and stated, "May 9, 2007, should be cited in the annals of cancer immunotherapy as Black Wednesday."
"Within an eight-hour period that day," he wrote, "the FDA succeeded in killing not one but two safe, promising therapies designed and developed to act by stimulating a patient's immune system against cancer."
Experts say, the new immunotherapies hold promise for many forms of cancer. "FDA's hubris will affect the lives and possibly the life spans of cancer patients from nearly every demographic, from elderly men with prostate cancer to young children with the rarest of bone cancers," according to Dr Thornton.
With the approval of the new therapies, the profits, along with the horrendous side effects of the only treatments now available, could become a thing of the past. "One day current treatment approaches such as surgery, radiation and chemotherapy, which often kill most but not all of a cancer, could be made obsolete by a potent immune response that eradicates the cancer cells and provides subsequent protection against return and relapse," Dr Thornton wrote.
As such, the new therapies pose a grave threat to the cancer industry as a whole, and the lost profits would not be limited to the sale of products. The pharmaceutical giants have spent a small fortune to gain control of every segment of the industry, from researchers to government regulators, and every year, billions of dollars flow through a nationwide network of research institutions and treatment providers under the guise of finding a cure for cancer.
However, the profits up for grabs have become so enormous that critics say the goal of industry-controlled research is no longer focused on finding a cure for cancer to save lives. Instead, the focus is on thwarting the development and approval of new therapies in order to protect the profits of the treatments already on the market.
The FDA's refusal to approve Provenge, a new immunotherapy vaccine manufactured by the Dendreon Corporation, has caused major outrage in the cancer community. Provenge supporters have sent thousands upon thousands of letters and other correspondence to the FDA, members of Congress, the Department of Justice and others.
In addition, the Ohio-based non-profit corporation, CareToLive, has filed a lawsuit on behalf of terminal cancer patients seeking a declaratory judgment that the FDA acted "arbitrarily" and "capriciously" by denying patients access to Provenge, in violation of their constitutional right to live.
Dendreon sought approval to treat late-stage androgen-independent prostate cancer (AIPC) patients who have no other options. A study presented to an FDA Advisory Committee at a March 29, 2007, meeting showed that, after 36 months, 34% of the men who received Provenge in a clinical trial were still alive, compared to only 11% of those who received a placebo.
Provenge is designed to stimulate the patient's own immune system to specifically attack only cancer cells, unlike chemo drugs that attack any fast-growing line of cells.
Patients who qualify for Provenge have already had their prostates removed or have undergone radiation and hormone therapy. Eligible patients receive a one-time round of treatment consisting of 3 visits to a urologist's or oncologist's office to give blood, and 3 visits for the blood enhanced with Provenge to be infused back into the body.
On September 10, 2007, CareToLive filed a motion asking the court to issue an order enjoining the FDA from denying the marketing and distribution of Provenge. The plaintiffs charge that within six months, another 15,000 patients will have died waiting for justice.
The memorandum filed with the motion points out that the only available treatment approved for terminal AIPC in the last 42 years is a chemo drug, Taxotere. "The effectiveness of Taxotere," it states, "is so superficial, and the side effects so severe, that most men decline the treatment, as the risks far outweigh the benefits."
According to the filing, between 300 and 600 patients per year die from the Taxotere treatment itself. "This is truly amazing," the memo states, "considering the cost of the treatment and the cost of hospitalization and that the average benefit is an increase in survival of only 2 ½ months."
In contrast, the Provenge safety profile is so good that nobody has died from it and less than one in four patients experience side effects consisting of mild flu-like symptoms lasting one or two days, the memo notes.
The defendants named in the lawsuit include Mike Leavitt, Secretary of the US Department of Health and Human Services; FDA Commissioner Andrew von Eschenbach; Dr Richard Pazdur, head of the FDA's Office of Oncologic Drug Division, and Dr Howard Scher, chosen by Dr Pazdur to serve on the advisory panel set up to review the approval of Provenge.
CareToLive is represented pro bono by Attorney Kerry Donahue, of the Dublin, Ohio law firm Bellinger & Donahue, while the FDA officials are represented by a legal team of 11 government attorneys, at last count, funded by tax dollars.
The plaintiffs allege that the defendants engaged in a conspiracy to prevent the approval of Provenge and that Dr Pazdur, "purposely located two conflicted oncologists who he was sure for a variety of reasons would be anti-Provenge and he instructed them to try to derail the approval of Provenge."
The plaintiffs charge that, by choosing Dr Scher, and also Dr Maha Hussain, to serve on the advisory panel, Dr Pazdur "likely found two of the most conflicted oncologists in the country to sit in judgment of Provenge, and who would both assuredly continue his plot to lobby others at the FDA to vote for non-approval."
At the behest of Dr Pazdur, and for their own future political and monetary gain, the plaintiffs claim, "these two oncologists did everything they could think of to obstruct and impede the approval of Provenge."
The waiver of conflicts of interest granted by the FDA to Dr Hussain, which allowed her sit on the panel, reveals that she is the lead investigator on a research contract awarded by a company that competes with Dendreon, and her husband owns stock in three competing companies valued at between $15,000 and $300,000.
The lawsuit alleges that, as part of the conspiracy, on May 9, 2007, the FDA denied terminally-ill patients access to Provenge, even though the FDA Advisory Committee recommended approval, found the vaccine safe by a 17-0 vote and found there was "substantial evidence" of efficacy with Provenge by a 13-4 vote.
In an attempt to derail an approval recommendation by the panel, the plaintiffs claim that, prior to the vote on efficacy, Dr Pazdur and "his co-conspirators changed the statutory question regarding efficacy from 'substantial evidence' to 'absolute certainty' of efficacy, in an effort to obtain a 'no' vote on Provenge."
However, during the voting, this manipulation was discovered and promptly corrected by the FDA's Dr Celia Witten and Dr Jesse Goodman, and by an overwhelming majority, the panel voted "yes" to the revised efficacy question.
"It is unprecedented for the FDA to overturn the Advisory Committee on such a positive vote when men are out of options, delaying approval and asking for more trials," according to CareToLive spokesman Mike Kearny in an August 2, 2007, press release.
"Men are dying now," he states. "They do not have years to wait."
In the case of Provenge's approval, the profits at stake could not be higher. Prostate cancer is the most common non-skin cancer in the US and the third most common cancer worldwide. More than one million men in the US have prostate cancer, with an estimated 232,000 new cases diagnosed each year and more than 30,000 men face death from the disease each year.
As an initial treatment, when diagnosed with prostate cancer, most men have their prostate removed, or undergo radiation, which can lead to various degrees of incontinence and impotence. After the initial treatments fails, hormone therapy is given to block the production of androgens such as testosterone, needed for cancer cells to grow, and some men undergo testicle removal in an attempt to stop the androgens from spreading the cancer.
With AIPC patients, prostate cancer has usually gone into remission and then returned, spreading to other parts of the body including the bones, lymph nodes, bladder, rectum, liver and lungs. All men who do not die of other causes progress to the final stage where the cells no longer respond to hormone therapy. Provenge is intended for use by patients who have already failed other types of therapy.
Because Taxotere is the only approved drug, Sanofi would have suffered the greatest immediate loss had Provenge been approved. According to firm's 2006 Annual Report, Taxotere was the company's 4th best-selling product in 2006, and the US is listed as the number one country contributing to sales.
As far as profits per dose, in the February 7, 2007, article, "What Does It Cost to Have Cancer?", a patient who received the chemo drug for breast cancer in 2006 reported that "each infusion of Taxotere cost over $16,000."
She also stated: "That's just for the drug, not administration or anything."
According to the lawsuit, defendant Dr Scher, Chief Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, is a scientific advisor and lead trial investigator for a competitor of Dendreon called Novacea. Under faculty disclosures at the University of Michigan, Dr Hussain is listed as an advisory board member of Novacea, and she receives research funding from Sanofi.
Dr Scher also has an interest in ProQuest Investments, which stood to reap windfall profits if Provenge was not approved. ProQuest is a venture capital fund established in 1998, in large part by Michael Milken, who was given the nickname "Junk Bond King," after being indicted on nearly 100 counts of insider trading and sentenced to 10 years in prison, in addition to being barred from the securities industry for life.
The ProQuest fund was established with a specific focus on prostate cancer, and SEC filings show that ProQuest and its principals are major shareholders of Novacea.
Citing documents from ProQuest, the plaintiffs allege that Dr Scher is a "ProQuest Executive" and "member of the Board of Directors", ProQuest reaps millions of dollars investing in prostate cancer companies based on advice from doctors such as Dr Scher, and ProQuest own stock in direct competitors including Novacea.
Dr Scher receives compensation from ProQuest as a scientific advisor recommending investments and for conducting clinical trials that result from the investments. He also holds an ownership interest in ProQuest.
The lawsuit also alleges that Dr Scher receives research support from the Prostate Cancer Foundation, as well as financial benefits, as one of a consortium of members who reviews new research on cancer drugs to determine which grants should be awarded by the Foundation.
The PCF, also founded by Mr Milken, is one of the largest sources of funding for the National Cancer Institute and government research programs. A following of the tangled web involved in the PCF reveals that Dr Jonathan Simons, President of the Foundation, Dr Stuart Holden, Medical Director, and Dr Howard Soule, an Executive Vice President of the Foundation, are all scientific advisors to ProQuest.
Another research arm found to be infested with several of the same insiders is the Prostrate Cancer Research Program, within the Department of Defense, which since 1997 has been appropriated a total of $730 million by Congress. According to a PCRP report, "Today, the PCRP is the second leading source of extramural prostate cancer research funding in the United States."
The PCRP funds a Clinical Consortium Award to support the creation of a major multi-institutional clinical trial resource, "to speed development of novel therapeutics that will ultimately decrease the impact of the disease."
Here, too, Dr Scher is listed as the leader of the consortium, and the list of participating clinical sites and lead investigators includes none other than Dr Hussain. Dr Simons is listed as developing new clinical therapeutics for late-stage prostate cancer, but a review of upcoming research listed in the report shows immunotherapies are not in the cards.
These consortium members are invaluable to the industry and investors due to their unique access to insider information about clinical trials and influence over the FDA approval process. Evidence of this claim came on May 30, 2007, less than 3 weeks after approval for Provenge was denied, when Novacea announced an agreement with Schering-Plough worth over $450 million, in which Schering agreed to jointly fund and develop Asentar, a competing prostate cancer drug, for which Dr Scher happens to be the lead investigator.
"The partnership leverages Novacea's existing capabilities with Schering-Plough's experienced development, regulatory and commercial teams and will provide Novacea with an opportunity to support the commercialization of Asentar in the United States," John Walker, company chairman and interim CEO, stated in a May 30, 2007 press release.
A May 2000 ProQuest document provides insight about the investment firm's interest in Asentar's success and states: "ProQuest Investments is a $100 million oncology-focused investment fund, partnered by Jeremy Goldberg and Jay Moorin."
Mr Moorin owned 1,910,988 shares of Novacea stock at the time of a May 15, 2006, SEC filing, and the ProQuest document mentions an investment from Domain Associates, "whose general partner, Jim Blair, has also worked with the fund to plot its strategy."
As it turns out, Mr Blair and Mr Moorin were both members of Novacea's board of directors when the Schering deal was set up. However, apparently their services are no longer needed, because on August 30, 2007, Novacea announced the resignation of James Blair and Jay Moorin, effective September 4, 2007, and September 19, 2007, respectively.
All that said, it does not take a financial genius to figure out that this whole deal could have gone up in smoke had Provenge been approved, because there would have been a drastic drop in the enrollment of late-stage cancer patients in clinical trials as soon as they learned that there was a new vaccine that could not only increase their survival rate but allow them to live out their final days without the agonizing side effects of chemotherapy.
Provenge's approval also would have caused many patients currently participating in trials to drop out. Novacea's 2006 Annual Report filed on April 2, 2007, less than 2 months before the Shering announcement, warned that the "clinical development and regulatory approval processes inherently contain significant risks and uncertainties."
The report shows Novacea was going broke trying to keep the Asentar trials running, with research and development expenses associated with the drug of $12.9 million for the year ended December 31, 2006, up from $7.3 million for the year ended December 31, 2005.
The $5.6 million increase was due primarily to the Phase 3 Asentar trial, and the filing warns that Novacea could experience many delays in getting its product to market due to problems in trials including, "patient enrollment may be slower than expected at trial sites due to factors including the limited number of, and substantial competition for, suitable patients with the particular types of cancer required for enrollment in our clinical trials".
It also notes that there "is a limited number of, and substantial competition for, suitable sites to conduct our clinical trials; clinical trial sites may terminate our clinical trials"; "patients and medical investigators may be unwilling or unable to follow our clinical trial protocols;" and "patients may fail to complete our clinical trials once enrolled."
In addition, another ongoing trial is evaluating Asentar as part of a combination therapy for AIPC patients with Sanofi's Taxotere. If safety or efficacy issues arise with Taxotere, the annual report warns, Novacea could experience significant regulatory delays, and the clinical trial may need to be terminated or redesigned.
Even if Asentar were to receive FDA approval, Novacea would continue to be subject to the risks that could arise with Taxotere or that Taxotere may be replaced as the standard of care for AIPC. "This could result in Asentar ™ being removed from the market or being less commercially successful," the report states.
Ironically, in one of 3 derogatory letters sent to the FDA urging the non-approval of Provenge leaked to the media following the failed efforts to rig the advisory panel vote, Dr Scher discussed the same fatal effects that the approval could have on the research industry. "An approval recommendation has far reaching implications beyond making the product available that the data simply do not support or justify," he wrote.
Approval would provide the Agency's endorsement of Provenge as a "standard of care" for men with AICP, he said, and by extension, elevate Provenge "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."
In other words, all the billions of dollars invested in the clinical trials now underway, or set to begin, conducted in hopes of gaining FDA approval for a new ACIP treatment, could go right down the drain if Provenge is approved as the first-line treatment for this patient population.
Dr Scher is probably more aware of this fact than anybody. On February 26, 2007, MedPage Today reported that in a satellite symposium titled, "Improving Upon Current Standards: The Integration of Novel Therapies in the Treatment of Androgen-Independent Prostate Cancer," sponsored by Novacea, Dr Scher said Taxotere-based combination therapy is being investigated in a dozen clinical trials for ACIP patients, and he reported receiving grants and research support from both Novacea and Sanofi.
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.
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.
Wednesday, July 28, 2010
The Holes in Bush's FDA
A Perpertual Leaker of Inside Dope
January 8, 2008 Evelyn Pringle
The steady leaking of insider information about products under review by the FDA has caused enormous losses for average American investors since the Bush Administration took control of the agency six years ago.
There are several ways that investors can profit from this type of insider information. The first is obvious, buy the stock because approval of a product will almost certainly raise a company's stock value. Investors who know about the decision ahead of time can bet the farm based on that information.
But investors who are tipped off that a product will not be approved can do the opposite. They can bet that company's stock value will fall by selling the stock short knowing full-well that the minute the news of non-approval becomes public, the stock's value will drop like a rock.
When the leaking of this type of information occurs, the losers are always the investors who play by the rules and make bets based on the best public information available. Unfortunately, in many instances, these are the very people who can least afford the loss.
One high-ranking member of the Bush Administration's FDA, Dr Richard Pazdur, has been one of the leakers in two cases involving cancer drugs that caused investors to lose vast amounts of money.
The first case devastated investors when a company's stock value dropped more than $1.5 billion in less than 3 weeks after Dr Pazdur tipped off the Cancer Leadership Council's legal counsel Samuel Turner that the FDA planned to reject the application for approval of a cancer drug the week before the decision was scheduled to be sent to the main sponsor, ImClone, on December 28, 2001.
At that time, Mr Turner also was a registered lobbyist for a number of pharmaceutical companies, including Bristol-Myers Squibb, which just happens to be the largest manufacturer of chemotherapeutic drugs.
Bristol-Meyer tipped off ImClone owners Harlan and Sam Waxal, and family members immediately started selling their stock. An investigation by the SEC later determined that the Waksals sold more than $10 million worth of stock in the 48 hours before the FDA's rejection of the application for drug was made public.
According to a June 16, 2002 report on Newsbytes News Network, short sellers also made millions by placing bets that ImClone's stock value would fall in the weeks before the FDA publicly rejected the application.
The House Committee on Energy and Commerce investigated the insider trading in this case, and a subcommittee held a hearing on June 13, 2002. At the start, the chairman noted that there were two stories here.
One, he said, "will be more fully told by the SEC and the Justice Department as it examines how the FDA process and what appears to be some rather amoristic players conspired in a way that allowed insider trading to potentially occur and an awful lot of investors to lose a lot of money while insiders were trading on information that was available only to them."
"The other story," he noted, "is about the process at FDA and how the FDA process allowed this to happen."
A transcript of the hearings shows that when members of Congress asked directly who within the FDA leaked the information to Bristol-Myers, Dr Pazdur and the rest of the Bush Administration officials talked in circles and never answered.
But in the end, somebody pulled some strings because Dr Pazdur got off Scott free, which probably accounts for his lack of fear when engaging in similar, behind-the-scenes activities in 2007.
In the more recent case, the continued short selling in Dendreon's stock following the Provenge Advisory Committee meeting of March 29, 2006, despite the fact that the Committee recommended approval of the drug, surely indicates that information leaked to Wall Street from inside the FDA guaranteed that the drug would not be approved.
On May 9, 2007, when Dendreon announced to the public that the FDA had issued the company a Complete Response Letter instead of an approval letter, the market value of Dendreon dropped more than 60% in one day.
The known people behind the "leaks" in this case are Dr Pazdur, along 2 members of the Advisory Committee who were chosen to participate on the panel by Dr Pazdur. When persons serve on these committees, they become "special government employees," and are subject to the same rules and regulations as all government employees.
When the Provenge Committee recommended approval, there were two votes taken. The first was on safety and the vote was 17-0 that the drug was safe. The second was on efficacy and the vote was 13-4 that the drug demonstrated "substantial evidence" of efficacy, the federally mandated standard.
The approval of this new cancer vaccine represented a grave threat to the multi-billion dollar chemotherapy industry. Dendreon is the first company to seek approval of a drug in a promising new class of immunotherapies that direct the body's own immune system to attack only cancer cells, unlike chemotherapy which destroys cancer cells but damages healthy cells and the immune system as well.
Provenge sought approval to treat men in the final stage of prostate cancer whose only option is months of chemotherapy with the drug Taxotere, which causes debilitating side effects and extends life on average 2.5 months.
In applying for approval, Dendreon submitted a study that showed 3 injections of Provenge extended life by nearly double that chemotherapy and the side effects, if any, consisted of flu-like symptoms for one or 2 days.
If the new immunotherapies turn out to be as effective as some experts claim, chemotherapy and radiation treatments could become obsolete in the not to distant future. Dr Pazdur knew this all too well. In fact, his fear was that if Provenge were to be approved, it would establish a new standard of care for late stage prostate cancer patients and from then on testing of new therapies would be up against Provenge.
He was also ticked off about the fact that the FDA had chosen the Center for Biologics Evaluation and Research to control the Provenge Advisory Committee instead of the Center for Drug Evaluation and Research, which he controlled.
So as a back-door means of regaining control, he recruited his two partners in crime, Dr Howard Scher, from the Memorial Sloan-Kettering Cancer Center, and Dr Maha Hussain, from Michigan University, to serve on the Advisory Committee to assist him in thwarting Dendreon's bid for the approval of Provenge.
Both of these doctors have made a fortune from their involvement in the cancer treatment and research racket over the past 2 decades. And they also stood to lose a fortune if the chemo-cartel was dismantled.
Investors had every reason to believe that Provenge would be approved once the Advisory Committee voted for approval. The FDA had never refused to follow a recommendation by its own experts to approve a drug for dying cancer patients who had no other options.
While testifying at the hearing, Dr David Penson, Associate Professor of Urology and Preventative Medicine at the University of Southern California, told the panel: "If you turn this drug down, it will likely set back the innovative field of active cellular immunotherapy in cancer many, many years."
He warned that the Committee's decision "will not only affect prostate cancer patients, but it may have an effect on the larger population of oncology patients in general."
Dr Hussain and Dr Scher were positioned on the panel to do everything in their power to make sure the vaccine was not approved. But their best efforts failed and within two weeks after the panel voted to approve the Provenge, Dendreon stock had nearly tripled in value and analysts were predicting that the vaccine could bring in $1 billion annually.
However, it was soon obvious that something was up, because the short sellers were still betting millions that the stock value would fall. On April 29, 2007, Bloomberg reported that shares were being sold short "at a record pace" as investors "bet the company's experimental prostate-cancer drug will fail to win approval from U.S. regulators."
All totalled, 33.9 million shares were sold short by the end of April. In hindsight, figuring out why people would engage in such risky betting was a no-brainer. The only people who could have known that Dendreon stock was headed for a nose-dive on May 9, 2007, because the FDA was going to overrule it's own panel by denying the approval of a cancer drug for dying patients for the first time in history, were the people who made it happen.
As late as May 7, 2007, Prohost Biotechnology, a firm that evaluates companies and publishes a monthly newsletter for investors, was calling Dendreon a good investment on its web site, stating: We Have A New Pick "DENDERON AGAIN."
The web site went on to explain why the firm was predicting that the short sellers were wrong in betting against the company, by stating in part:
This time, positive investors/analysts are determined to neutralize the shorters' efforts. Why not, if the verdict is expected in 10 days only and the committee, which was appointed by the FDA itself has already voted 17-0 in favor of safety and 13-4 in favor of efficacy?
We are with the approval, Prohost said. "As a matter of fact, we expect it on May 15, based on many facts, the most important is the result of the FDA committee's voting."
The firm noted that the experts on the panel would not have been chosen by the FDA if they were not highly regarded researchers, medical doctors, and academicians, and stated:
"If the results of voting would have been 50-50, we would have understood the need for the FDA to take a stand. But with a landslide voting in favor of approval, we do not see why the FDA should hesitate to follow the committee's recommendation of approval.
"Besides, the vaccine is safe. It acts synergistically with the available treatments and it helped desperate patients survive advanced prostate cancer."
But as it turns out, another plot was put in action immediately after the news came out that the panel recommended approval, in which government officials at the FDA and the National Cancer Institute worked with Dr Scher, and probably Dr Hussain, to compose letters with bogus reasons why the FDA should not follow the recommendation.
Once the rough drafts were edited, the letters were sent to the FDA by email and hardcopy, and leaked for publication on the internet by "The Cancer Letter," which just happens to be the same rag used to leak insider information in the ImClone case.
The overly dramatic Dr Scher, even went so far as to tell Thomas Fleming, another doctor who just happened to send a letter to the FDA, disparaging Provenge, which was also put out on the internet by "The Cancer Letter," that he could not sleep because he was so concerned over the possibility of patients being harmed if Provenge was approved and that's why he wrote the letter. Dr Fleming then noted that he could not sleep either.
This is an utterly ridiculous remark coming from Dr Scher, considering that he and Dr Hussain voted with the majority 17-0 that Provenge was safe at the hearing.
The pharmaceutical companies that stood to benefit the most from the non-approval of Provenge were Novacea, Schering-Plough and Sanofi-Aventis because they have billions of dollars invested in research, drug trials, and cancer treatments involving therapies that would compete directly with Provenge for the same late stage prostate cancer patients.
Dr Scher and Dr Hussain, as well as her husband, are involved in dozens of studies conducted by the same companies. Both Dr Scher and Dr Hussain are consultants and members of the scientific advisory board for Novacea, which produces Asentar together with Schering-Plough.
Asentar would directly compete with Provenge and at the time of the Advisory Committee hearing, Dr Scher was the co-lead investigator on trials of Asentar
According to www.portfolio.com, Dr Scher is also an officer, member of the Board of Directors, and a member of the Scientific Advisory Board of ProQuest Investments, which was had mega-bucks invested in Novacea during 2007. However, for some odd reason, ProQuest's web site no longer lists the names for the Scientific Advisory Board.
Dr Scher and Dr Hussain have also both received research funding from Sanofi-Aventis the maker of Taxotere.
A review of Dr Hussain's most current resume in fact, shows that she's been on one long global junket funded by the cancer treatment and research racket for close to 2 decades. She apparently began her journey in Bagdad, Iraq, in1980, and 2 years later she was in the UK and a year after that she ended up in Detroit, Michigan.
It looks like her home base has been Ann Arbor, Michigan since late 2002, that is in between her 6 trips to Canada, 3 to Hawaii, 3 to Puerto Rico, 2 to St Thomas, 2 to Barcelona, and at least 1 trip to Japan, China, Jordon, Lisbon, Monte Carlo, Bermuda, and Austria, in addition to her 17 trips to California, 9 to Chicago, 4 to New Orleans, 5 to New York, 9 to Florida, and at least 38 trips to other states.
The list of excursions certainly demonstrates that the good doctor enjoyed quite a lot of travel on someone else's dime. In fact, her hotel fees alone would put a bonifide hooker to shame.
Its impossible to determine the amount of "research" funding funneled her way because the amount is redacted for half of the grants listed. But at a bare minimum, she had at least 28 million "current" reasons to sabotage the approval of Provenge.
Under "Current Grant Support," she lists 11 grants, although 5 have no amounts. But the total for the other 6 comes to over $28 million, and she will be receiving income from a few of these grants for several more years.
Dr Hussain also lists another 2 grants as submitted, with all information redacted. She lists 5 under "Active Research," all involving treatments for late stage prostate cancer, but not one includes the amount. No dates are listed for these 5 grants either, which makes it impossible to estimate how long she intends to profit from this research.
The doctor also lists 30 funding sources under "Past", but only 6 have amounts. The total for those 6 comes to more than $20 million, so it would probably be safe to say that if all amounts were to be listed, Dr Hussain had at least 100 million good reasons to derail the approval of Provenge.
All the plotting by persons benefiting from the non-approval of Provenge might have gone undetected if not for the non-profit advocacy group, Care-To-Live. The group filed a lawsuit in Federal court against officials in charge of the FDA, including Dr Pazdur and Dr Scher, seeking an injunction to overturn the FDA's decision and to make Provenge available immediately to extend the lives of dying prostate cancer patients.
By filing the lawsuit, the group was able to gain access to a lot of information and after reading much of it, one thing's for sure, the government officials involved in this sick plot will never be accused of wasting time on the clock worrying about dying cancer victims.
Another case of leaking occurred on March 1, 2006, when the FDA sent a letter to the Canadian investment firm, Infinium Capital, that said the agency would allow testing for a generic version of Vancocin, marketed by ViroPharma, to be conducted in a test tube.
Two weeks later, after allowing plenty of time for persons with the inside information to position themselves to make a killing in the stock market, Infinium issued a report on ViroPharma stating, "Generics . . . sooner than you think".
According to an SEC filing by ViroPharma, Infinium's report was the first public disclosure of the new testing standard and:
"ViroPharma itself had not previously heard that OGD had lowered its BE standard for Vancocin. Nor it would seem, except those to whom OGD had privately communicated, had anyone else."
ViroPharma's filing went on to note that Infinium's report stated:
"Our recent communications with the FDA regarding the approval process for a potential generic competitor to Vancocin lead us to believe a generic could enter the market 1-2 years sooner than current expectations."
What "recent communications with FDA" might mean, the filing states, beyond the March 1, 2006 letter to Infinium, is unclear to ViroPharma. On March 16, 2006, Medindia.com dropped a bombshell when it informed the public of the news by quoting analysts at Infinium as saying it could mean a generic version would be available by early 2008.
"Previously, generic manufacturers may not have been interested in developing this therapeutic due to its low revenue potential; however, with the recent sales growth of 133 percent in 2005, Vancocin is now on the radar screen," an Infinium analyst told Medindia.
Infinium's announcement caused shares of ViroPharma "to dip by about 33 percent," according to Medindia. But in fact, Infinium's report triggered a multi-day stock sell-off that cut the company's market capitalization by 40%, or roughly $500,000,000.
The approval process prior to the FDA's unexpected announcement required trials to be conducted on humans. ViroPharma has filed a Petition to stop the approval of generic versions with allegations that the FDA violated the Freedom of Information Act, the Data Quality Act, the Administrative Procedure Act, and its own Standards of Conduct.
Vancocin is used to treat hospital-acquired bacterial infections in the lower gastrointestinal tract caused by the bacterium Clostridium difficile. In order to be effective, the drug must be released in one specific section of the intestines, making its release mechanism far more difficult to replicate than other drugs.
The release of an ineffective version of Vancocin at this point in time would be especially dangerous because recent studies have shown that cases of Clostridium difficile-associated disease (CDAD) are increasing world-world. The disease causes 400,000 cases of diarrhea and colitis each year in the US, according to the US Department of Veterans Affairs.
In addition, a paper by Michel Warney, et al., entitled, "Toxin Production by an Emerging Strain of Clostridium difficile Associated with Outbreaks of Severe Disease in North America and Europe," in the September 2005 Lancet medical journal, reported a new strain of C difficile that produces up to 23 times more toxins than previous strains; this strain has been implicated as the cause of a more severe form of the disease
A May 11, 2007, report by the Pennsylvania Health Care Cost Containment Council said that in 2005, patients with CDAD were hospitalized 2-and-a-half times longer, charged over twice as much, and were 4 times as likely to die as patients without the disease.
On average, the report notes, patients with CDAD remain in the hospital almost 7 days longer at a cost of $73,576, verses the average charge of $30,833 for patients without the disease. A November 2007 report entitled, "The Emerging Infectious Challenge of Clostridium difficile-Associated Disease in Massachusetts Hospitals: Clinical and Economic Consequences," cites a "conservative estimate" of the annual cost for CDAD management in the US as $3.2 billion.
People treated with antibiotics are at the highest risk because antibiotics disrupt the balance of bacteria in the GI tract, which allows C difficile bacteria to multiply. CDAD is highly infectious and can spread by contact with patients or touching surfaces contaminated with C difficile spores. The severity of the disease ranges from mild cases of diarrhea to painful colitis, bloodstream infections or death.
Years ago, CDAD was almost exclusively limited to patients in hospital or long-term care settings where infectious diseases spread easily. But there are now widespread reports of patients developing CDAD outside hospital settings, referred to as "community-acquired" CDAD, and with no antibiotic exposure.
Recent studies indicate that many cases may be caused by proton pump inhibitor drugs which inhibit the production of gastric acid in the stomach that acts as a defense against bacteria and spores, widely used by persons with ulcers and other GI illnesses.
The December 21, 2005, Journal of American Medical Association published a report by Canadian researchers based on studies that determined that gastric acid-suppressant drugs were associated with the rising cases of community-acquired CDAD.
The researchers used the United Kingdom General Practice Research Database and identified all 1,672 cases of CDAD recorded between 1994 and 2004 and found that 1,233, or 74%, of the patients had not been hospitalized in the year prior to the diagnosis and were considered community-acquired.
The study showed the increase in community-acquired cases rose from less than 1 per 100,000 in 1994 to 22 per 100,000 in 2004 and during this same period, prescriptions for antibiotics had decreased while prescriptions for proton pump inhibitors had increased.
The first course of treatment for CDAD caused by antibiotics is to stop the antibiotics. But if diarrhea continues and becomes severe, Vancocin is a treatment of last resort for very sick patients which means there is no room for error.
The FDA claims that dissolution testing for the generic version can be done by creating a test tube solution that replicates the environment in the lower intestine. But experts say it would be next to impossible to replicate the GI tracts of very ill and elderly patients to determine whether the generic version will work the same in the targeted area.
Experts also point out that drug interactions, such as those in patients on proton pump inhibitors would make it hard to develop a solution that would replicate the GI tract.
The approval of an ineffective generic version of Vancocin, will subject millions of people to potentially fatal risks because the patients who end up being treated with this medication will have no second chances if it fails.
The FDA is currently under attack for doing the exact same thing by not requiring adequate testing for the generic version of the antidepressant Wellbutrin. The FDA approved the generic in 2006 and after a steady stream of patients reported that they were experiencing serious side effects, testing by ConsumerLabs, revealed that the time release rate of the active ingredient was much faster than the release rate in the original drug.
The consumer-product testing group, ConsumerLab began investigating the drug after Joe and Terry Graedon, authors of The People's Pharmacy column, came to the group with complaints received from readers of their column. While the Graedons had received complaints about generic drugs before, "we had never received this volume of response," Joe Graedon, a pharmacologist, told MSNBC on October 12, 2007.
"In almost all cases people were saying their depression returned," he said. Users also complained about severe headaches, digestive problems, insomnia, anxiety, and tremors.
ConsumerLab performed dissolution testing on 6 samples of each medication and found that even though both contained the same amount of the active ingredient, the generic released nearly 50% of the ingredient in the first 4 hours verses 25% by Wellbutrin.
"It's been an eye-opener for everyone," ConsumerLab President, Dr Tod Cooperman, told MSNBC. "It makes you question whether generics are always going to be equivalent to the original product."
"If these things are releasing at such different rates," he advised, "it's hard to believe they'd be acting the same way in your body."
"It would seem very difficult to imagine that the results we saw would be acceptable results," Dr Cooperman told MSNBC.
He pointed out that the release of the active ingredient more quickly could mean there is less medication available to the patient later, and may explain why patients experienced a return of their depression.
He said a time-release problem might also explain why patients experienced more side effects, such as headache, irritability and nausea, if they received a high dose of the medicine upfront. "Too much Wellbutrin can cause side effects, even the potential for seizure," he told MSNBC.
The Canadian firm Biovial filed a petition with the FDA in 2005, asking the agency to require generic makers to conduct more rigorous testing of generic versions of Wellbutrin prior to their approval but apparently the agency ignored the request.
An agency spokesperson told MSNBC that the FDA does not require generic makers to do clinical trials on hundreds or thousands of people as required for name brand drugs. It only requires lab data and "bioequivalence" testing in about 24 to 36 healthy volunteers showing that the drug enters the bloodstream in a similar manner to the original product.
Since the generic version was approved, millions of consumers have switched to the drug to save money which means a high number of patients may be experiencing serious side effects without knowledge of the cause. Experts say this whole problem could have been avoided had testing on humans been conducted to check the release mechanism before millions of scripts were written.
"Sustained release mechanisms are not that easy to develop, and they tend to be proprietary in nature," Michael Katz, clinical associate professor of pharmacy practice and science at the University of Arizona College of Pharmacy told MSNBC.
"It would be difficult for a generic manufacturer to reproduce the same release characteristics as the brand-name product," he stated.
"Such differences clearly could have an impact on patients," he said, "and my view is that sustained-release products are among the relatively short list of products that should not be switched."
Experts say the time release characteristics would be even more difficult to replicate in a generic version of Vancocin, where the concern is not just about how much of the drug is released into the blood stream but rather in one specific section of the GI tract.
The leaking of information in the Vancocin case is reminiscent of a major scandal that erupted during the first Bush Administration in 1989, when FDA officials were charged with taking bribes from generic makers and sharing insider information.
On August 28, 1989, Time magazine reported that an investigation by the Justice Department had uncovered evidence that "some makers of generic pharmaceuticals falsified laboratory test results and paid off FDA chemists to gain quick Government approval for their products."
In that case, Charles Chang the head of the FDA's generic division and two co-workers pleaded guilty to accepting a total of $24,300 in illegal gifts in exchange for preferential treatment for certain generic makers in July 1989, according to the Time report.
In the end, the generic scandal during the first Bush Administration landed Mr Chang in federal prison and caused 42 others and 10 companies to be convicted on charges of fraud and corruption and the FDA Commissioner Frank Young resigned in November 1989.
The crooks in the current Bush Administration's FDA deserve the same fate.
January 8, 2008 Evelyn Pringle
The steady leaking of insider information about products under review by the FDA has caused enormous losses for average American investors since the Bush Administration took control of the agency six years ago.
There are several ways that investors can profit from this type of insider information. The first is obvious, buy the stock because approval of a product will almost certainly raise a company's stock value. Investors who know about the decision ahead of time can bet the farm based on that information.
But investors who are tipped off that a product will not be approved can do the opposite. They can bet that company's stock value will fall by selling the stock short knowing full-well that the minute the news of non-approval becomes public, the stock's value will drop like a rock.
When the leaking of this type of information occurs, the losers are always the investors who play by the rules and make bets based on the best public information available. Unfortunately, in many instances, these are the very people who can least afford the loss.
One high-ranking member of the Bush Administration's FDA, Dr Richard Pazdur, has been one of the leakers in two cases involving cancer drugs that caused investors to lose vast amounts of money.
The first case devastated investors when a company's stock value dropped more than $1.5 billion in less than 3 weeks after Dr Pazdur tipped off the Cancer Leadership Council's legal counsel Samuel Turner that the FDA planned to reject the application for approval of a cancer drug the week before the decision was scheduled to be sent to the main sponsor, ImClone, on December 28, 2001.
At that time, Mr Turner also was a registered lobbyist for a number of pharmaceutical companies, including Bristol-Myers Squibb, which just happens to be the largest manufacturer of chemotherapeutic drugs.
Bristol-Meyer tipped off ImClone owners Harlan and Sam Waxal, and family members immediately started selling their stock. An investigation by the SEC later determined that the Waksals sold more than $10 million worth of stock in the 48 hours before the FDA's rejection of the application for drug was made public.
According to a June 16, 2002 report on Newsbytes News Network, short sellers also made millions by placing bets that ImClone's stock value would fall in the weeks before the FDA publicly rejected the application.
The House Committee on Energy and Commerce investigated the insider trading in this case, and a subcommittee held a hearing on June 13, 2002. At the start, the chairman noted that there were two stories here.
One, he said, "will be more fully told by the SEC and the Justice Department as it examines how the FDA process and what appears to be some rather amoristic players conspired in a way that allowed insider trading to potentially occur and an awful lot of investors to lose a lot of money while insiders were trading on information that was available only to them."
"The other story," he noted, "is about the process at FDA and how the FDA process allowed this to happen."
A transcript of the hearings shows that when members of Congress asked directly who within the FDA leaked the information to Bristol-Myers, Dr Pazdur and the rest of the Bush Administration officials talked in circles and never answered.
But in the end, somebody pulled some strings because Dr Pazdur got off Scott free, which probably accounts for his lack of fear when engaging in similar, behind-the-scenes activities in 2007.
In the more recent case, the continued short selling in Dendreon's stock following the Provenge Advisory Committee meeting of March 29, 2006, despite the fact that the Committee recommended approval of the drug, surely indicates that information leaked to Wall Street from inside the FDA guaranteed that the drug would not be approved.
On May 9, 2007, when Dendreon announced to the public that the FDA had issued the company a Complete Response Letter instead of an approval letter, the market value of Dendreon dropped more than 60% in one day.
The known people behind the "leaks" in this case are Dr Pazdur, along 2 members of the Advisory Committee who were chosen to participate on the panel by Dr Pazdur. When persons serve on these committees, they become "special government employees," and are subject to the same rules and regulations as all government employees.
When the Provenge Committee recommended approval, there were two votes taken. The first was on safety and the vote was 17-0 that the drug was safe. The second was on efficacy and the vote was 13-4 that the drug demonstrated "substantial evidence" of efficacy, the federally mandated standard.
The approval of this new cancer vaccine represented a grave threat to the multi-billion dollar chemotherapy industry. Dendreon is the first company to seek approval of a drug in a promising new class of immunotherapies that direct the body's own immune system to attack only cancer cells, unlike chemotherapy which destroys cancer cells but damages healthy cells and the immune system as well.
Provenge sought approval to treat men in the final stage of prostate cancer whose only option is months of chemotherapy with the drug Taxotere, which causes debilitating side effects and extends life on average 2.5 months.
In applying for approval, Dendreon submitted a study that showed 3 injections of Provenge extended life by nearly double that chemotherapy and the side effects, if any, consisted of flu-like symptoms for one or 2 days.
If the new immunotherapies turn out to be as effective as some experts claim, chemotherapy and radiation treatments could become obsolete in the not to distant future. Dr Pazdur knew this all too well. In fact, his fear was that if Provenge were to be approved, it would establish a new standard of care for late stage prostate cancer patients and from then on testing of new therapies would be up against Provenge.
He was also ticked off about the fact that the FDA had chosen the Center for Biologics Evaluation and Research to control the Provenge Advisory Committee instead of the Center for Drug Evaluation and Research, which he controlled.
So as a back-door means of regaining control, he recruited his two partners in crime, Dr Howard Scher, from the Memorial Sloan-Kettering Cancer Center, and Dr Maha Hussain, from Michigan University, to serve on the Advisory Committee to assist him in thwarting Dendreon's bid for the approval of Provenge.
Both of these doctors have made a fortune from their involvement in the cancer treatment and research racket over the past 2 decades. And they also stood to lose a fortune if the chemo-cartel was dismantled.
Investors had every reason to believe that Provenge would be approved once the Advisory Committee voted for approval. The FDA had never refused to follow a recommendation by its own experts to approve a drug for dying cancer patients who had no other options.
While testifying at the hearing, Dr David Penson, Associate Professor of Urology and Preventative Medicine at the University of Southern California, told the panel: "If you turn this drug down, it will likely set back the innovative field of active cellular immunotherapy in cancer many, many years."
He warned that the Committee's decision "will not only affect prostate cancer patients, but it may have an effect on the larger population of oncology patients in general."
Dr Hussain and Dr Scher were positioned on the panel to do everything in their power to make sure the vaccine was not approved. But their best efforts failed and within two weeks after the panel voted to approve the Provenge, Dendreon stock had nearly tripled in value and analysts were predicting that the vaccine could bring in $1 billion annually.
However, it was soon obvious that something was up, because the short sellers were still betting millions that the stock value would fall. On April 29, 2007, Bloomberg reported that shares were being sold short "at a record pace" as investors "bet the company's experimental prostate-cancer drug will fail to win approval from U.S. regulators."
All totalled, 33.9 million shares were sold short by the end of April. In hindsight, figuring out why people would engage in such risky betting was a no-brainer. The only people who could have known that Dendreon stock was headed for a nose-dive on May 9, 2007, because the FDA was going to overrule it's own panel by denying the approval of a cancer drug for dying patients for the first time in history, were the people who made it happen.
As late as May 7, 2007, Prohost Biotechnology, a firm that evaluates companies and publishes a monthly newsletter for investors, was calling Dendreon a good investment on its web site, stating: We Have A New Pick "DENDERON AGAIN."
The web site went on to explain why the firm was predicting that the short sellers were wrong in betting against the company, by stating in part:
This time, positive investors/analysts are determined to neutralize the shorters' efforts. Why not, if the verdict is expected in 10 days only and the committee, which was appointed by the FDA itself has already voted 17-0 in favor of safety and 13-4 in favor of efficacy?
We are with the approval, Prohost said. "As a matter of fact, we expect it on May 15, based on many facts, the most important is the result of the FDA committee's voting."
The firm noted that the experts on the panel would not have been chosen by the FDA if they were not highly regarded researchers, medical doctors, and academicians, and stated:
"If the results of voting would have been 50-50, we would have understood the need for the FDA to take a stand. But with a landslide voting in favor of approval, we do not see why the FDA should hesitate to follow the committee's recommendation of approval.
"Besides, the vaccine is safe. It acts synergistically with the available treatments and it helped desperate patients survive advanced prostate cancer."
But as it turns out, another plot was put in action immediately after the news came out that the panel recommended approval, in which government officials at the FDA and the National Cancer Institute worked with Dr Scher, and probably Dr Hussain, to compose letters with bogus reasons why the FDA should not follow the recommendation.
Once the rough drafts were edited, the letters were sent to the FDA by email and hardcopy, and leaked for publication on the internet by "The Cancer Letter," which just happens to be the same rag used to leak insider information in the ImClone case.
The overly dramatic Dr Scher, even went so far as to tell Thomas Fleming, another doctor who just happened to send a letter to the FDA, disparaging Provenge, which was also put out on the internet by "The Cancer Letter," that he could not sleep because he was so concerned over the possibility of patients being harmed if Provenge was approved and that's why he wrote the letter. Dr Fleming then noted that he could not sleep either.
This is an utterly ridiculous remark coming from Dr Scher, considering that he and Dr Hussain voted with the majority 17-0 that Provenge was safe at the hearing.
The pharmaceutical companies that stood to benefit the most from the non-approval of Provenge were Novacea, Schering-Plough and Sanofi-Aventis because they have billions of dollars invested in research, drug trials, and cancer treatments involving therapies that would compete directly with Provenge for the same late stage prostate cancer patients.
Dr Scher and Dr Hussain, as well as her husband, are involved in dozens of studies conducted by the same companies. Both Dr Scher and Dr Hussain are consultants and members of the scientific advisory board for Novacea, which produces Asentar together with Schering-Plough.
Asentar would directly compete with Provenge and at the time of the Advisory Committee hearing, Dr Scher was the co-lead investigator on trials of Asentar
According to www.portfolio.com, Dr Scher is also an officer, member of the Board of Directors, and a member of the Scientific Advisory Board of ProQuest Investments, which was had mega-bucks invested in Novacea during 2007. However, for some odd reason, ProQuest's web site no longer lists the names for the Scientific Advisory Board.
Dr Scher and Dr Hussain have also both received research funding from Sanofi-Aventis the maker of Taxotere.
A review of Dr Hussain's most current resume in fact, shows that she's been on one long global junket funded by the cancer treatment and research racket for close to 2 decades. She apparently began her journey in Bagdad, Iraq, in1980, and 2 years later she was in the UK and a year after that she ended up in Detroit, Michigan.
It looks like her home base has been Ann Arbor, Michigan since late 2002, that is in between her 6 trips to Canada, 3 to Hawaii, 3 to Puerto Rico, 2 to St Thomas, 2 to Barcelona, and at least 1 trip to Japan, China, Jordon, Lisbon, Monte Carlo, Bermuda, and Austria, in addition to her 17 trips to California, 9 to Chicago, 4 to New Orleans, 5 to New York, 9 to Florida, and at least 38 trips to other states.
The list of excursions certainly demonstrates that the good doctor enjoyed quite a lot of travel on someone else's dime. In fact, her hotel fees alone would put a bonifide hooker to shame.
Its impossible to determine the amount of "research" funding funneled her way because the amount is redacted for half of the grants listed. But at a bare minimum, she had at least 28 million "current" reasons to sabotage the approval of Provenge.
Under "Current Grant Support," she lists 11 grants, although 5 have no amounts. But the total for the other 6 comes to over $28 million, and she will be receiving income from a few of these grants for several more years.
Dr Hussain also lists another 2 grants as submitted, with all information redacted. She lists 5 under "Active Research," all involving treatments for late stage prostate cancer, but not one includes the amount. No dates are listed for these 5 grants either, which makes it impossible to estimate how long she intends to profit from this research.
The doctor also lists 30 funding sources under "Past", but only 6 have amounts. The total for those 6 comes to more than $20 million, so it would probably be safe to say that if all amounts were to be listed, Dr Hussain had at least 100 million good reasons to derail the approval of Provenge.
All the plotting by persons benefiting from the non-approval of Provenge might have gone undetected if not for the non-profit advocacy group, Care-To-Live. The group filed a lawsuit in Federal court against officials in charge of the FDA, including Dr Pazdur and Dr Scher, seeking an injunction to overturn the FDA's decision and to make Provenge available immediately to extend the lives of dying prostate cancer patients.
By filing the lawsuit, the group was able to gain access to a lot of information and after reading much of it, one thing's for sure, the government officials involved in this sick plot will never be accused of wasting time on the clock worrying about dying cancer victims.
Another case of leaking occurred on March 1, 2006, when the FDA sent a letter to the Canadian investment firm, Infinium Capital, that said the agency would allow testing for a generic version of Vancocin, marketed by ViroPharma, to be conducted in a test tube.
Two weeks later, after allowing plenty of time for persons with the inside information to position themselves to make a killing in the stock market, Infinium issued a report on ViroPharma stating, "Generics . . . sooner than you think".
According to an SEC filing by ViroPharma, Infinium's report was the first public disclosure of the new testing standard and:
"ViroPharma itself had not previously heard that OGD had lowered its BE standard for Vancocin. Nor it would seem, except those to whom OGD had privately communicated, had anyone else."
ViroPharma's filing went on to note that Infinium's report stated:
"Our recent communications with the FDA regarding the approval process for a potential generic competitor to Vancocin lead us to believe a generic could enter the market 1-2 years sooner than current expectations."
What "recent communications with FDA" might mean, the filing states, beyond the March 1, 2006 letter to Infinium, is unclear to ViroPharma. On March 16, 2006, Medindia.com dropped a bombshell when it informed the public of the news by quoting analysts at Infinium as saying it could mean a generic version would be available by early 2008.
"Previously, generic manufacturers may not have been interested in developing this therapeutic due to its low revenue potential; however, with the recent sales growth of 133 percent in 2005, Vancocin is now on the radar screen," an Infinium analyst told Medindia.
Infinium's announcement caused shares of ViroPharma "to dip by about 33 percent," according to Medindia. But in fact, Infinium's report triggered a multi-day stock sell-off that cut the company's market capitalization by 40%, or roughly $500,000,000.
The approval process prior to the FDA's unexpected announcement required trials to be conducted on humans. ViroPharma has filed a Petition to stop the approval of generic versions with allegations that the FDA violated the Freedom of Information Act, the Data Quality Act, the Administrative Procedure Act, and its own Standards of Conduct.
Vancocin is used to treat hospital-acquired bacterial infections in the lower gastrointestinal tract caused by the bacterium Clostridium difficile. In order to be effective, the drug must be released in one specific section of the intestines, making its release mechanism far more difficult to replicate than other drugs.
The release of an ineffective version of Vancocin at this point in time would be especially dangerous because recent studies have shown that cases of Clostridium difficile-associated disease (CDAD) are increasing world-world. The disease causes 400,000 cases of diarrhea and colitis each year in the US, according to the US Department of Veterans Affairs.
In addition, a paper by Michel Warney, et al., entitled, "Toxin Production by an Emerging Strain of Clostridium difficile Associated with Outbreaks of Severe Disease in North America and Europe," in the September 2005 Lancet medical journal, reported a new strain of C difficile that produces up to 23 times more toxins than previous strains; this strain has been implicated as the cause of a more severe form of the disease
A May 11, 2007, report by the Pennsylvania Health Care Cost Containment Council said that in 2005, patients with CDAD were hospitalized 2-and-a-half times longer, charged over twice as much, and were 4 times as likely to die as patients without the disease.
On average, the report notes, patients with CDAD remain in the hospital almost 7 days longer at a cost of $73,576, verses the average charge of $30,833 for patients without the disease. A November 2007 report entitled, "The Emerging Infectious Challenge of Clostridium difficile-Associated Disease in Massachusetts Hospitals: Clinical and Economic Consequences," cites a "conservative estimate" of the annual cost for CDAD management in the US as $3.2 billion.
People treated with antibiotics are at the highest risk because antibiotics disrupt the balance of bacteria in the GI tract, which allows C difficile bacteria to multiply. CDAD is highly infectious and can spread by contact with patients or touching surfaces contaminated with C difficile spores. The severity of the disease ranges from mild cases of diarrhea to painful colitis, bloodstream infections or death.
Years ago, CDAD was almost exclusively limited to patients in hospital or long-term care settings where infectious diseases spread easily. But there are now widespread reports of patients developing CDAD outside hospital settings, referred to as "community-acquired" CDAD, and with no antibiotic exposure.
Recent studies indicate that many cases may be caused by proton pump inhibitor drugs which inhibit the production of gastric acid in the stomach that acts as a defense against bacteria and spores, widely used by persons with ulcers and other GI illnesses.
The December 21, 2005, Journal of American Medical Association published a report by Canadian researchers based on studies that determined that gastric acid-suppressant drugs were associated with the rising cases of community-acquired CDAD.
The researchers used the United Kingdom General Practice Research Database and identified all 1,672 cases of CDAD recorded between 1994 and 2004 and found that 1,233, or 74%, of the patients had not been hospitalized in the year prior to the diagnosis and were considered community-acquired.
The study showed the increase in community-acquired cases rose from less than 1 per 100,000 in 1994 to 22 per 100,000 in 2004 and during this same period, prescriptions for antibiotics had decreased while prescriptions for proton pump inhibitors had increased.
The first course of treatment for CDAD caused by antibiotics is to stop the antibiotics. But if diarrhea continues and becomes severe, Vancocin is a treatment of last resort for very sick patients which means there is no room for error.
The FDA claims that dissolution testing for the generic version can be done by creating a test tube solution that replicates the environment in the lower intestine. But experts say it would be next to impossible to replicate the GI tracts of very ill and elderly patients to determine whether the generic version will work the same in the targeted area.
Experts also point out that drug interactions, such as those in patients on proton pump inhibitors would make it hard to develop a solution that would replicate the GI tract.
The approval of an ineffective generic version of Vancocin, will subject millions of people to potentially fatal risks because the patients who end up being treated with this medication will have no second chances if it fails.
The FDA is currently under attack for doing the exact same thing by not requiring adequate testing for the generic version of the antidepressant Wellbutrin. The FDA approved the generic in 2006 and after a steady stream of patients reported that they were experiencing serious side effects, testing by ConsumerLabs, revealed that the time release rate of the active ingredient was much faster than the release rate in the original drug.
The consumer-product testing group, ConsumerLab began investigating the drug after Joe and Terry Graedon, authors of The People's Pharmacy column, came to the group with complaints received from readers of their column. While the Graedons had received complaints about generic drugs before, "we had never received this volume of response," Joe Graedon, a pharmacologist, told MSNBC on October 12, 2007.
"In almost all cases people were saying their depression returned," he said. Users also complained about severe headaches, digestive problems, insomnia, anxiety, and tremors.
ConsumerLab performed dissolution testing on 6 samples of each medication and found that even though both contained the same amount of the active ingredient, the generic released nearly 50% of the ingredient in the first 4 hours verses 25% by Wellbutrin.
"It's been an eye-opener for everyone," ConsumerLab President, Dr Tod Cooperman, told MSNBC. "It makes you question whether generics are always going to be equivalent to the original product."
"If these things are releasing at such different rates," he advised, "it's hard to believe they'd be acting the same way in your body."
"It would seem very difficult to imagine that the results we saw would be acceptable results," Dr Cooperman told MSNBC.
He pointed out that the release of the active ingredient more quickly could mean there is less medication available to the patient later, and may explain why patients experienced a return of their depression.
He said a time-release problem might also explain why patients experienced more side effects, such as headache, irritability and nausea, if they received a high dose of the medicine upfront. "Too much Wellbutrin can cause side effects, even the potential for seizure," he told MSNBC.
The Canadian firm Biovial filed a petition with the FDA in 2005, asking the agency to require generic makers to conduct more rigorous testing of generic versions of Wellbutrin prior to their approval but apparently the agency ignored the request.
An agency spokesperson told MSNBC that the FDA does not require generic makers to do clinical trials on hundreds or thousands of people as required for name brand drugs. It only requires lab data and "bioequivalence" testing in about 24 to 36 healthy volunteers showing that the drug enters the bloodstream in a similar manner to the original product.
Since the generic version was approved, millions of consumers have switched to the drug to save money which means a high number of patients may be experiencing serious side effects without knowledge of the cause. Experts say this whole problem could have been avoided had testing on humans been conducted to check the release mechanism before millions of scripts were written.
"Sustained release mechanisms are not that easy to develop, and they tend to be proprietary in nature," Michael Katz, clinical associate professor of pharmacy practice and science at the University of Arizona College of Pharmacy told MSNBC.
"It would be difficult for a generic manufacturer to reproduce the same release characteristics as the brand-name product," he stated.
"Such differences clearly could have an impact on patients," he said, "and my view is that sustained-release products are among the relatively short list of products that should not be switched."
Experts say the time release characteristics would be even more difficult to replicate in a generic version of Vancocin, where the concern is not just about how much of the drug is released into the blood stream but rather in one specific section of the GI tract.
The leaking of information in the Vancocin case is reminiscent of a major scandal that erupted during the first Bush Administration in 1989, when FDA officials were charged with taking bribes from generic makers and sharing insider information.
On August 28, 1989, Time magazine reported that an investigation by the Justice Department had uncovered evidence that "some makers of generic pharmaceuticals falsified laboratory test results and paid off FDA chemists to gain quick Government approval for their products."
In that case, Charles Chang the head of the FDA's generic division and two co-workers pleaded guilty to accepting a total of $24,300 in illegal gifts in exchange for preferential treatment for certain generic makers in July 1989, according to the Time report.
In the end, the generic scandal during the first Bush Administration landed Mr Chang in federal prison and caused 42 others and 10 companies to be convicted on charges of fraud and corruption and the FDA Commissioner Frank Young resigned in November 1989.
The crooks in the current Bush Administration's FDA deserve the same fate.
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