My Anger with the FDA

I woke this morning feeling very angry and much stressed. One of the principles in cancer management is to reduce, ideally remove stress from ones life. Now the FDA is adding stress, major stress to my life.

When I heard about the FDA action I was disappointed, but not angry. As the evening went on I felt increasing disappointment, but not anger. Just prior to going to bed I received an e-mail from another prostate cancer advocate asking that we make a strong response to the FDA’s failure to approve Provenge. I immediately let him know that I was on board.

Then this morning I woke up. I realized that I was no longer just disappointed; I was upset and very angry. I felt Angry at my cancer, angry at the lack of options to treat the cancer and mostly angry at my government for standing in the way and blocking my ability to make my own informed decision on my own treatment.

I don’t understand how this all can be true, but I do know that I am very, very angry.

The following appeared in today’s Wall Street Journal:

FDA Delays Approving Cancer Vaccine

Dismayed Prostate Patients

To Launch Flood of Protests;

A Question of Efficacy

By MARILYN CHASE

May 10, 2007

Patient activists, stunned by a Food and Drug Administration decision to put off approval of a promising new prostate-cancer vaccine, vowed to shower the agency with protest emails as part of a continued push for early access to the experimental treatment.

The FDA late Tuesday asked Dendreon Corp. to provide more data to support the claim that its prostate-cancer vaccine called Provenge works to prolong survival. The company has a 500-patient study now under way to answer that question. But FDA’s so-called approvable letter could mean another two years at least until the product reaches patients.

“My mind is bouncing around. I feel very, very let down,” said Steve Fleischmann, a Seattle businessman whose 2003 diagnosis at age 47 launched him on a career in advocacy that began in his hospital bed as he recovered from prostate surgery. His activist group Survivors Celebration raised $4 million in research funding for the nonprofit Prostate Cancer Research Institute. “What does this say to men who have prostate cancer and want to stay alive?” Mr. Fleischmann asked.

The decision was a bitter defeat for patient advocates, many of whom attended an FDA advisory panel on March 29 wearing blue lapel ribbons

— a symbol of prostate-cancer activism — to speak in favor of the vaccine. Their presence was credited with helping win over the panel, which voted 13-4 in favor of recommending approval, even though evidence from two clinical trials was weak in showing benefit. Mr.

Fleischmann called on every man with prostate cancer to send an email to the FDA to protest its refusal to go along with the panel’s recommendation.

Prostate cancer is expected to strike 218,000 American men in 2007, and to cause an estimated 27,500 deaths in the U.S. Provenge is designed to treat a subset of men — estimated at 45,000 to 55,000 — with advanced cancer that is spreading and is no longer responsive to hormone blockers. The main alternatives include radiation and Taxotere, a chemotherapy drug. But these treatments generally are considered to have limited duration and toxic side effects.

Prostate-cancer advocates seized on Provenge as a hopeful new approach — and one they wanted to see available even after only limited study. Their efforts echo growing calls by patients with a range of afflictions for quicker access to promising medicines. When lives are at stake, the argument goes, patients can’t afford to wait for enough data to be gathered to do a rigorous analysis of risks and benefits. Groups advocating for Alzheimer’s disease patients are similarly planning campaigns to press the FDA to move quickly to make drugs for that debilitating condition available. The strategy recalls campaigns by AIDS patients in the early 1990s that successfully persuaded regulators to make AIDS drugs available much sooner than conventional standards for approval would allow.

But a resurgence of patient activism comes at a time when the FDA is also under pressure from other critics who believe it has been too quick to approve drugs and too cozy with the industry it regulates.

In the case of Provenge, both of the studies submitted to make the case for approval failed to meet their primary “endpoints” — the target findings that would have proven the vaccine slowed the growth of the tumor. And while the panel unanimously vouched for the safety of Provenge, the agency was concerned about hints of an increased number of strokes among patients taking the vaccine.

But an unconventional analysis of the data — looking at findings that had not been the original endpoints of the trials — suggested patients taking the drug lived 4� months longer than those who didn’t. Advocates seized on that number to advance their position in support of approval.

Provenge is the first candidate in a new approach to cancer treatment called immunotherapy. It is referred to as a “vaccine” because it is intended to marshal the body’s immune system into attacking the tumors.

‘Open to Anything’

In Sanibel, Fla., prostate-cancer advocate Jan Manarite, who leads an advocacy group called Raise a Voice and whose husband is battling advanced prostate cancer, vowed to redouble her educational campaign.

She said Raise a Voice is evaluating in the next day or so whether to join Mr. Fleischmann’s email campaign and is planning other actions including press releases and meetings with other activist organizations.

“We’re open to anything that serves these men with prostate cancer,”

she said in an interview. “Our commitment is unwavering.”

But their push for expanded access to Provenge will leave many empty handed for now. Dendreon’s CEO Mitchell Gold, calling the FDA move “extremely disappointing,” said the company will move to finish its 500-patient study — the only way patients can get access for now.

Asked whether Dendreon will offer compassionate access to nonstudy participants, Dr. Gold said, “No, the company does not have that kind of resources. We look forward to completing the trial and working with the FDA to bring the drug to patients that way.” Dr. Gold said he expects an interim analysis in 2008 with final data in 2010.

Volatile Dendreon stock which has traded in the $4 to $25 range over the past year had surged after an FDA advisory panel recommended that the agency approve licensure based on early data. Yesterday shares plunged 64% to $6.33 on Nasdaq.

A major point of tension in the deliberations over Provenge was the company’s claim that the drug added 4� months of survival. “A 4.5- month life extension probably doesn’t sound like a lot to those of you who are blessedly healthy,” Joel Novak of Brooklyn, N.Y., testified at the advisory panel hearing. “But to me, this is a 20% extension of my life expectancy.”

Analysis Criticized

Critics pointed out that the problem with Dendreon’s claim was that it came from an unplanned analysis of a 127-patient study that failed to meet its primary goal. Such “sub-analyses” aren’t generally considered to be statistically valid. One panel member, prostate- cancer researcher Maha Hussain of the University of Michigan, during the panel hearing called it “incredibly under-powered.”

After the favorable panel vote, Howard Scher, a prominent prostate- cancer researcher at Memorial Sloan Kettering Cancer Center, New York, and a panel member who voted against approval, wrote a letter to FDA officials urging rejection of the Provenge licensing application. The letter, leaked to The Cancer Letter, an influential newsletter, prompted furious protests in emails posted on blogs and Web sites.

Data and Evidence

“We want Provenge to work; that’s our raison d’etre,” Dr. Scher said in a recent interview. But “they need to complete the study.”

Yesterday following word that the FDA essentially followed his advice, Dr. Scher said, “I think that was the correct decision. At the end of the day, it’s the data and the evidence. It’s not an emotional decision.”

Paul Goldberg, editor of The Cancer Letter, said “FDA didn’t have much of a choice.” Basing decisions on reliable evidence, he added, is also “patient advocacy. This is just another form of it through science.”

None of this assuages Mr. Fleischmann. The father of two children, ages 5 and 9, he recently experienced a return of his cancer. “I’m on seven weeks of radiation starting June 1,” Mr. Fleischmann said.

“Let’s say I get my cancer back again. Then my options are chemo or Provenge.” He added: “I don’t want to go on a study. I don’t want a placebo. I want the drug.”

Joel T. Nowak, MA, MSW