A site to advocate for “Provenge Now!” has been launched. Provenge is Dendreon’s immunotherapy for prostate cancer, which was approved 17-0 for safety and 13-4 for efficacy by an FDA Advisory Committee vote March 29th this year. On May 9, Dendreon announced that FDA has sent them a “Complete Response Letter,” commonly called an approvable letter, requesting more data. Dendreon CEO Mitchell Gold said “The FDA has requested additional clinical data in support of the efficacy claim.”

In today’s Wall Street Journal, Mark Thornton, M.D., Ph.D. deplores the FDA’s decision on Dendreon’s sipuleucal-T immunotherapy (Provenge vaccine). Dr. Thornton says “May 9, 2007, should be cited in the annals of cancer immunotherapy as Black Wednesday. Within an eight-hour period that day, 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. The 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.”

Dendreon’s CEO Mitchell Gold traded some of his stock during the high period following the FDA Advisory panel vote on his company’s prostate cancer immunotherapy sipuleucal-T (Provenge). Gold told the WSJ Health blog that he sold “less than 20%” of his holdings in the company following the upbeat FDA advisory panel vote. “it’s all public,” he said, without elaborating.

More of a surprise is to see that Steve Fleischmann, one the patients who spoke passionately to the FDA committee, did the same:

Before the stock tanked some savvy investors cashed in. One of them was businessman Steve Fleischmann, who became a prostate cancer patient, activist and Dendreon shareholder all in the same year. “I bought Dendreon in 2003;I’ve owned it for years,” he told the Health Blog. But he shed some of his shares after Dendreon surged at the end of March on a panel of experts’ recommendation that FDA approve the vaccine. He declined to quantify his holdings or profits, but said, “I wanted to take some of my chips off the table so I wasn’t so invested. It’s natural.”

Still, Fleischmann decried the protracted tug of war among investors in the company: “The sad thing is that Dendreon became more of a stock play than a humanistic play — a game between longs and shorts — and all about padding people’s pockets.”

Wall Street Journal Health Blog

Raise a Voice, an advocacy group for advanced prostate cancer patients, which is calling for patient access to drugs that have passed through Phase I trials, has written a thank you letter to the FDA Advisory Committee on Dendreon’s sipuleucel-T (Provenge).

Dr. Thomas R. Fleming, Ph.D., a prostate cancer survivor and nationally recognized statistician specializing in clinical trials design and analysis, has written a letter urging FDA officials not to approve Dendreon’s application at this time.

Echoing concerns about post-hoc analysis expressed by FDA statistical reviewer Dr. Bo-Guang Zhen, Fleming disagrees with a prostate cancer survivor on the FDA’s March 29 advisory committee who said that Dendreon’s sipuleucel-T (Provenge) vaccine offers "an opportunity to make a choice."

Fleming writes: "As a fellow person living with prostate cancer I strongly disagree with [this] statement that all patients want is a ‘choice.’ Patients want an ‘informed choice.’”

A few days before the FDA Advisory Committee hearing March 29 on Provenge (sipuleucal-T), Thomas Farrington, a leading African-American prostate cancer survivor advocate, wrote an urgent plea. Farrington, who is President and Founder of Prostate Health Education Network (PHEN), wrote:

With a death rate 140% higher than for other men, coupled with a comparable level of suffering and quality of life loss, our need for new and innovative treatments is desperate and unparalleled relative to any other type of cancer in terms of the death rate disparity.

Last September — a month celebrated annually as Prostate Cancer Awareness Month — Farrington’s group PHEN helped organize a 2-day, Washington, D.C. African American Prostate Cancer Disparity Summit. This event was sponsored by Dana-Farber Cancer Center, TAP Pharmaceuticals, and Dendreon Corp. and a fourth sponsor, The Pharmaceutical Research and Manufacturers of America (PhRMA), which represents the country’s leading pharmaceutical research and biotechnology companies.

This event brought together a range and depth of physicians, scientists, lawmakers, religious leaders, industry representatives and professional and volunteer prostate cancer patient advocates. Yet its agenda ended up focused rather narrowly on prostate cancer vaccines as a solution to disparities. The 2-day event was structured around four main topics:

1. Why the African American Prostate Cancer Disparity?
2. Outreach for Education, Awareness and Advocacy…What Works?
3. Early Detection Screening: The Benefits, Risks and Debate
4. Prostate Cancer Vaccines: Immunotherapy…the Promise of a Cure?

The session on prostate cancer vaccines aimed “to bring into focus the status and progress of immunotherapy as a prostate cancer treatment option.” At that time vaccines for prostate cancer were not a treatment option, they were in clinical trials. Panelists were invited to explore “how success in this area could impact the elimination of the racial disparity and how this treatment compares to others that are currently available.” Lead speaker for this session was Mitchell H. Gold, MD, President and CEO, Dendreon Corporation.

Is the company taking steps beyond sponsoring patient advocacy activities to assure equal access to the vaccine if and when it is approved? Well, yes, but whether these are solid steps must be examined.

Dr. Andrew von Eschenbach, M.D., Director of the FDA, who is an oncologist, surgeon and cancer survivor, often uses the metaphor of a building a bridge between the promise of science and technology and the delivery of drugs, or “interventions,” that can “eradicate” diseases including cancer, diabetes and Alzheimer’s disease. “Together we can build that bridge,” he said in 2006. “We can build a bridge that links discovery and development of new drugs and biologics and medicine with their delivery to all people.” Dr. von Eschenbach envisions a transformation of the FDA into a science-based and science-led institution:

we must envision an FDA that will not only be a science-based regulatory agency, but that will be a science-led facilitating agency, which helps new products come across that bridge of development more rapidly, in much larger volumes, ready to be delivered to patients.

But as Bob Samuels brought up at the FDA Advisory panel hearing March 29th, African-American prostate cancer patients were under-represented in the clinical trials for Provenge. While Dendreon’s role in the Summit encouraged African American men to believe that a vaccine may help resolve some of their direst cancer care access problems, the company has not even tested this product on a fair representation of African American patients.

Dendreon’s representative om the 2006 African American Prostate Cancer Disparity Summit’s advisory board was Christopher Lockett, who by then was the company’s Director of Government Relations. LAst month Lockett was promoted to the position of a senior director of government affairs. Locket will be “responsible for managing Dendreon’s relationships with local, state and federal government officials.” Primarily he will be responsible for “Dendreon’s interactions with the Centers of Medicare and Medicaid Services (CMS) regarding potential future coverage of Provenge, and provide counsel and direction on coding and reimbursement for the product.”

If Provenge is approved Medicare and Medicaid coverage of the vaccine will be vital for men with advanced prostate cancer who lack private health insurance. The current estimated price for Provenge is around $30,000. Before and after receiving Provenge, most patients will be expected to remain on androgen ablation drugs like Lupron or Zoladex; some will take bisphosphonates to counteract osteoporotic effects of the androgen loss induced by Lupron and Zoladex, and some will go on to take chemotherapy as soon as Provenge fails to control the cancer or ceases doing so, which may happen within weeks.

So Medicare and Medicaid coverage is absolutely essential and will follow if the FDA approves the vaccine. A second accessibility factor of concern for advanced prostate cancer patients is convenient access to a clinic or hospital qualified to administer powerful anti-cancer drugs. This is especially an issue with chemotherapy. For patients in rural areas or distant suburbs, a weekly or 3-weekly trip to anything approaching a “center of excellence” for chemotherapy may entail arduous, heroic efforts or may be foreclosed by lack of a driver, extreme distance or impassible weather conditions.

A third factor to consider with regard to Dendreon’s preparations for dealing with Medicare and Medicaid is the company’s natural desire for rapid market penetration.

Is Mr. Lockett’s role at Dendreon part of this highway to the future? Do his qualifications for the job make him a bridge toward overcoming of entrenched, systemic disparities in our health care system? Mr. Lockett joined Dendreon from TAP Pharmaceutical Products Inc., where, Dendreon says, “he most recently served as director of government affairs. He spent the majority of his 17-year career at TAP providing strategic counsel to the company on the impact of state and federal programs, including Medicare and Medicaid, as well as legislative issues on TAP’s two leading products.”

One of TAP’s leading products is Lupron, an androgen-blockade, or therapeutic castration, drug of a class that has dominated treatment for men with advanced prostate cancer since the late 1980s.

During Mr. Lockett’s 17-year stint at TAP in the ’90′s, TAP was charged with health care crimes against Medicare. In 2001 the company agreed to pay $875 million to settle charges. “As part of a condition for doing business in the future with providers who are members of the Medicare and Medicaid programs, TAP agreed to enter into an extensive Corporate Integrity Agreement. That agreement provides for significant training of TAP’s sales and marketing employees and changes in supervision and controls.”

“Chris is an expert in health care policy issues management,” said James Caggiano, Dendreon’s vice president of sales and marketing, to whom Lockett will report, “particularly with respect to prostate cancer medicines, and will play an important role in ensuring that our commercialization strategy is aligned with current and evolving policies that could affect PROVENGE.”

When Provenge vaccine for prostate cancer is approved by the FDA, as most likely it will be on or by May 15, this decision to make this new therapy available immediately to any patient who can afford or whose insurance covers it — rather than to delay approval until the results are in from a larger clinical trial — will be due to Michael Milken. In Cora Daniels’ blockbuster article for Fortune Magazine (November 2004), The Man Who Changed Medicine, reprinted at Cptech.com, Milken said:

I believe the person who waits for 110% of the facts to be in and all the information is a person who is probably not alive — because it’s too late for him. A lot of businesspeople have been forced to make decisions without 100% or perfect information but based on what they know. I worked in a field where ten seconds was a long decision process. Either you’re buying the securities or you’re not. Either you’re selling them or you’re not. Now people said, ‘Well, gosh, that’s a short period of time,’ and I say, ‘No, it’s not.’ I’ve prepared my entire life to make that decision. I think getting off that inertia of making a decision qualifies well in building something.

Dr. Maha Hussain (left) is calling for an open access program for Dendreon’s Provenge prostate cancer vaccine (Sipuleucel-T) pending completion of an ongoing, 500 man clinical trial, She made this suggestion March 29 during the FDA Advisory Committee hearing after voting “No” on the vaccine’s efficacy. She followed up with a letter to the FDA reiterating her “No” position and again calling for an open access program.

Dr. Hussain is the second oncologist among 4 members of the panel who voted “No” to the efficacy of the drug who has followed up with a letter to the FDA.

Dr. Maha Hussain, an oncologist who was one of 4 out of 17 members of the FDA Advisory Committee to vote against accepting against the company’s claim to efficacy for Provenge (Sipuleucel-T) prostate cancer vaccine, is calling for an expanded access program to empower patients who want and need it to receive the drug while an ongoing 500 man clinical trial of Provenge is completed.

Reviewing Proveng’s chances of FDA approval from the point of view of investors, Matthew Herper gives an overview useful for patients as well. Herper writes:

The FDA has a legal deadline of May 15 to make a decision–although it is possible to break or extend it. But buying the stock in front of this deadline is probably highly risky. There is a reasonable chance the FDA will decide to go against the panel vote and ask for more data. And the downside to the stock if the FDA does delay approval by asking Dendreon for more data is probably much bigger than any potential gain.