Will the New FDA Commissioner Please Stand Up?

Just in case you have been living in a cave for the last few weeks, allow me to bring you up to speed on who will be the next FDA Commissioner.

Before you get too excited, President elect Obama has not disclosed his choice to lead the FDA.  However, that has not stopped many from speculating, wishing, or suggesting.  Just today, Pharma Marketing News revealed the results of its fourteen pages "Who should be the next FDA Commissioner" survey http://www.news.pharma-mkting.com/Article-PMN710-04.pdf . 

Two weeks ago the WSJ reported http://online.wsj.com/article/SB122843198339081041.html that Bart Stupak (D., MI) sent a letter to President elect Obama urging him not to appoint anyone at the FDA.

I even jumped into the fray with this open letter to President elect Obama: 

This is a Hail Mary and if by some chance this reaches your and the transition team’s hands, all I can say is "finally, score one for the little guy.”

I am not a huge advocacy or special interest group but I believe as Dr. Martin Luther King once said, “Almost always, the creative dedicated minority has made the world better.” I am one of the dedicated minorities trying to make this world a better place for our children.

There have been a lot of rumors floating around about the new FDA Commissioner. Most recently, a letter was penned by Representative Stupak to President Elect Obama transition team regarding Janet Woodcock. We agree with Representative Stupak and would like to add our voices.

President elect Obama ran a grassroots campaign on change. If the new administration is about change and I whole heartily believe it is, Dr. Woodcock's nomination would be more of the status quo. She is a career bureaucrat, very cozy with big pharma, and one of THE problems at the top of the FDA.

When searching for replacements at the FDA, I respectfully urge you to look for individuals without ties to lobbyists, special interest groups, and big pharma. The FDA needs a complete overhaul of its top officials. Fresh officials with fresh ideas and the willingness to look at new therapies with fresh eyes are needed. Dr. Susan F. Wood comes to mind.

The FDA has gone seriously astray in its evaluation of efficacy in new drug/biologic license applications, slavishly applying a form of statistical purity when they should be asking whether the statistical evidence demonstrates efficacy using a reasonable medical probability standard.

As a result, many life-saving drugs are delayed in gaining approval by a number of years, the cost of developing drugs has skyrocketed prohibitively, far fewer drugs are being developed because of the increased expense, and far fewer drugs are being approved (but not because of safety concerns). Focus on safety (a legitimate concern, but which is separate from efficacy, and which, like efficacy, must be viewed in context of the type of condition being treated) has obscured this problem. There is a significant need to reverse this current obsession (with statistical purity) when evaluating efficacy, and such an adjustment does not have to lessen safety evaluation and post approval safety monitoring. FDA needs a new commissioner who understands that FDA's role in efficacy evaluation has evolved into a monster that the agency is not equipped to manage, has ignored Congress' intent, and has poorly served patients by delaying marketing of safe drugs that have been shown by good evidence to be effective in prolonging life in late stage diseases. Ultimately, patients are losing. The Provenge story is a symptom of the infectious disease at the FDA.

Provenge is an immunotherapy for late stage prostate cancer that was to represent the first in a new class of active cellular immunotherapy treatments approved in the United States. Such approval was thought to be the beginning of a new era where a more effective way to treat many forms of cancer would commence. The immunotherapy involves three visits to an Urologist’s office where a patient’s cells are collected, treated, and infused back into the patient. Essentially, the process trains the body’s own immune system to recognize the cancer and fight it.

Why is this case different and why the urgency? In this case, patients are missing a treatment that has been through a decade of testing, proceeded through phase one, phase two, and two phase three trials, all under the guidance of the FDA, been reviewed by FDA clinicians and determined to be worthy of Fast Track Status, been accepted for final and complete filing was reviewed by FDA clinicians and determined to be worthy of Priority Review Status, and granted a hearing overseen by a panel of 17 outside experts. An expert panel overwhelmingly agreed that it is safe and that it has demonstrated substantial evidence of efficacy (congressionally mandated standard). Never before has the FDA overturned a positive FDA expert panel recommendation to approve a drug for an end stage disease.

Inquiries by advocates, media, and others to the FDA have failed to obtain a specific reason why the FDA would over rule their advisory committee (AC) and not timely approve Provenge. The FDA has a complete lack of transparency and accountability. One agency PR person stated that they decided to go along with two of the AC members who voiced concerns about approval. It was discovered that those two AC members had both disclosed and undisclosed conflicts of interest. Quite possibly, both conflicted doctors would benefit career wise and financially by delaying Provenge approval.

Following that discovery, Reps. Michael H. Michaud (D-Maine), Dan Burton (R-Ind.), and Tim Ryan (D-Ohio) on Dec. 12, 2007 asked the House Energy and Commerce Committee to investigate the FDA's review of Provenge. Chairman Dingell and Representative Pallone decided not to investigate because they bought into the FDA pronouncement that it is an ongoing process and not a final decision. Therefore, the process should not be disturbed, since they may one day approve Provenge. What Dingell and Pallone did not recognize was that the decision by the FDA to delay Provenge was final for tens of thousands of men and their families.

Oncologist, Dr. Mark Thornton dubbed the day Provenge and Junovan approval were denied as “Black Wednesday,” stating “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.” He went on to say, “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.” Another noted Urologist said, “A terrible mistake has been made” by the FDA. Other advocacy groups held protests first in Washington, DC at the Capitol, then at the FDA in Rockville, and later in ten other cities across the country denouncing the decision. A citizen petition was filed in July 2007 asking the FDA to reconsider its wrongful decision and has yet to be decided or properly responded to by the FDA. Several petitions were then sent to Congress, one from an ad hoc group called Physicians for Provenge asking for reconsideration of the denial of Provenge and a congressional hearing.

The majority of Urologists that have reviewed the data think that Provenge should be approved immediately, along with many past FDA chiefs. Interestingly the FDA says they would allow the company to give away Provenge on a case-by-case basis just not sell it. The procedural nightmare of 90,000 applications to Dendreon and prohibitive cost of a small company like Dendreon to produce and distribute Provenge combined with the then inability of Urologists to treat all the patients without reimbursement of expenses, make this impossible as the FDA well knows. However, it does beg the question, why is Provenge worthy of being given away but prohibited a license to be marketed and distributed to the patients as other kinds of treatments are?

On October 6, 2008, Dendreon, the manufacture of Provenge sent out a press release detailing results at the interim peak of the ongoing IMmunotherapy for Prostate AdenoCarcinoma Treatment (IMPACT) trial. The results confirmed what we, who have been following this story, already knew: Provenge is safe and most importantly, it saves lives. The IMPACT trial data is blinded to Dendreon. However, the Independent Data Monitoring Committee (IDMC) reported a 20% decline in the death rate in the Provenge arm compared to the placebo.

The FDA was not impressed. The FDA seems to value their strict statistics over saving lives. Accordingly, based on those strict statistics, the FDA wanted to see the death rate decreased by 22%. Yes, you read that correctly. Twenty-two percent versus 20% statistical requirement in a group of men with advanced stage prostate cancer. Where is the common sense and compassion in that?

Unfortunately, the prostate cancer advocacy groups do not have the power and money that breast cancer groups and other cancer advocacy groups have, despite the fact that Prostate cancer is the second leading cause of cancer death. Also unfortunately, the larger prostate cancer groups depend so much on their fundraising that they try not to publicly support any particular treatment for fear of political fall out hurting their fundraising capability, especially when they originally supported failed competitors and do not want to admit to mistakes . The largest prostate cancer advocacy group, Prostate Cancer Foundation has in fact supported competitors to Provenge that have since failed in their trials and have invested in the success of rivals to the detriment of Provenge and to the very patients they are supposed to serve.

Some important facts should be pointed out about how our Veterans are affected by Prostate Cancer. The rate of post-surgical prostate cancer recurrence among white veterans rose by 42 percent if they had been exposed to Agent Orange, compared to non-exposed veterans. Black veterans exposed to the herbicide fared even less well, with a recurrence rate that was 75 percent higher than their non-exposed peers were. Moreover, when prostate cancer did recur among veterans exposed to Agent Orange, it seemed that they had a much shorter PSA doubling time, a surrogate for aggressiveness. Among black men with a cancer recurrence, PSA levels doubled in just nine months for those exposed to Agent Orange, compared to 16 months for those unexposed to the toxin.

A huge number of Veterans have late stage prostate cancer. They fought for us yet we have an FDA that cannot even be bothered to be responsive to our concerns.

Source: Vietnam Agent Orange & Responsibility Campaign web site
http://www.vn-agentorange.org/healthday_20070520.html

Lastly but certainly not least, this issue should be of special concern to African American men and their families because they are disproportionately prone to dying of prostate cancer. An estimated 30,770 cases of prostate cancer are expected to occur among African American men in 2005, accounting for approximately 42% of all cancers diagnosed in this population. Between 1997 and 2001, the prostate cancer incidence rate was on average 60% higher in African American men than in white men.

Prostate cancer is the second leading cause of cancer deaths in African American men. It is estimated that 5,050 deaths from prostate cancer will occur in African American men in 2005. African American men have the highest mortality rate of any ethnic and racial group in the US. The death rate from prostate cancer is 2.4 times higher in African Americans than in white men. The 5-year survival rate drops to 29% when the cancer has spread to distant sites (LATE STAGE). Provenge is designed for these late stage cancer patients.

*(Information excerpted from; American Cancer Society, Cancer Facts & Figures
for African Americans 2005-2006.)

The new commissioner needs to be briefed on this situation if he/she is not already aware of it. Many of those that will be considered for the position are aware of the Provenge debacle but unless the importance of the issue can be presented and explained to the new commissioner, timely action is unlikely to occur. Time is of the essence for the 90,000 men who are prostate cancer survivors now and future prostate cancer survivors. The FDA needs to respond to the concerns of the Citizens on this issue but to date they have been unwilling to do what common sense dictates and that is to speed Provenge to the patients who so desperately need it. As an advocate, patients contact me wanting access to Provenge and I have to tell them that they cannot get Provenge until the FDA allows it, which at the current pace may be 2010 or later. Since most men diagnosed as late stage need to be immediately given Provenge for it to work most effectively (it acts more like a vaccine and takes time to ramp up) such a response is a death sentence.

We personally have met several of the patients that were in a small Provenge study conducted seven years ago and they are still alive. One told us this year that he was going on a fishing trip with his friends. Another one, who is 80 plus years old, has told me that he is still working, driving, and very independent. He credits his good health to receiving Provenge. More men should be allowed to spend more time with their children and grandchildren.

Please make this issue a priority of the administration and use your knowledge of the situation when deciding on a new FDA commissioner, to expedite approval of Provenge, and investigate the Provenge advisory panel meeting. If nothing else, these actions would restore the public’s confidence in our Food and Drug regulatory system.