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In Depth May 21, 2008, 3:50PM EST

Cancer's Cruel Economics

(page 2 of 3)

Dr. Oleg Loran is a big fan of a drug developed in the U.S. but available only in Russia Alexander Gronsky

Pazdur, head of the FDA's cancer drug division, says patients should come first Chad Dowling

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The ultimate authority on whether these methods will pass muster is the FDA's Office of Oncology Drug Products, headed by Dr. Richard Pazdur, one of the most powerful men in medicine. An oncologist who formerly practiced at M.D. Anderson Cancer Center in Houston, Pazdur is demanding and decisive. His division typically gives no quarter when clinical trials produce equivocal results. Pazdur says this is only fair to patients, the constituency he serves: "Efficacy, efficacy, efficacy. That's what we're looking for."

Only the Sickest Patients

Not all patients agree that Pazdur has their best interests at heart. Some advocacy groups, angry at the lack of new cancer drugs, went all the way to the U.S. Supreme Court last year in an attempt to force the FDA to let people buy almost any experimental cancer drug being tested in humans. The Court refused to hear their appeal, but the groups haven't relented. On May 30, the FDA will face a nationwide protest led by CareToLive, a nonprofit advocacy group angered by the agency's rejection last year of Provenge, a controversial prostate cancer vaccine made by Dendreon (DNDN). It would have been the first new drug for prostate cancer in 20 years, and an outside panel of cancer experts chosen by the FDA recommended approval, but the agency asked for another clinical trial.

Pazdur rejects the attacks, pointing out that the FDA already allows patients access to any experimental cancer drug on a "compassionate use" basis if standard treatment options have been exhausted. The agency, he says, is routinely made a scapegoat by both patients and company executives who refuse to abandon a drug despite an obvious lack of efficacy. "Believe me, if there were a clear survival effect, the drug would be approved," says Pazdur.

Establishing such a clear effect is exceedingly difficult. The FDA wants proof that a cancer drug keeps patients alive longer, although it will consider other markers for efficacy, such as a delay in tumor growth. But clinical trials usually enroll only the sickest patients, few of whom live more than a few months even when a drug works. If healthier patients were tested, it could take five years or more of follow-up to show that a drug helped them live longer.

Those difficulties haven't kept the pharmaceutical industry from trying. There are currently some 750 cancer drugs in human trials, far more medications than in other disease categories. Successfully ushering any one of these drugs through the necessary development stages will take up to 15 years and typically cost more than $1 billion—about $200 million more than is spent winning approval for a noncancer drug.

The clinical trial sinkhole most threatens small biotechs that develop the bulk of new cancer drugs, and it is these firms that complain the loudest about the FDA. Pazdur responds that, while a large pharmaceutical company may be willing to cut its losses if a clinical trial isn't panning out, startups with no other products in their pipelines too often keep a drug in development long after failure is apparent. "If they have one drug, it's their baby," he says. "They can't let go of the drug because that's the end of the company."

Antigenics CEO Garo Armen vigorously defends his own persistence. His crusade for the drug Oncophage is personal: His mother suffered from breast cancer for years. When he was 17, Armen emigrated with her from Turkey to New York and searched for a cure, but she died four months later.

Armen, now 55, eventually landed on Wall Street as a pharmaceutical analyst, and started his own health-care investment fund in 1989. Four years later he was contacted by Pramod Srivastava, then a biochemist at Mount Sinai School of Medicine, about a cancer vaccine he had developed. The treatment involved removing a few of the patient's tumor cells, isolating and fortifying the cellular proteins that normally alert the immune system to disease, and reinjecting the proteins into the patient.

"I Feel Very, Very Fortunate"

Armen embraced the idea and in 1994 started Antigenics with $250,000 of his own money, plus the backing of a few friends. He was initially stirred by the results from animal testing; the vaccine cured 80% of mice in the early stages of cancer with virtually no side effects. It did not work as well on large tumors, an ominous sign of troubles to come. Still, early human tests were sufficiently promising that Armen was able to take Antigenics public in February, 2000, at $18 a share, raising $72.5 million. A few months later the FDA agreed to review the vaccine on an accelerated schedule when the company filed for approval, and Antigenics began recruiting 728 patients with kidney cancer for the phase III trial.

Enlisting patients was no easy task. Fewer than 5% of U.S. cancer patients participate in clinical trials, and only 39,000 Americans are diagnosed with kidney cancer each year. Antigenics had to scour the world for patients.

Ultimately, 118 cancer centers participated in the trial, 63 of them outside the U.S. The largest group of patients, 172, was treated in Russia. In the U.S., Dr. Christopher Wood of M.D. Anderson Cancer Center in Houston was lead investigator of the Oncophage trial, and he became a keen advocate. "There is clear evidence that it works," he says, pointing to the case of Steven Creel of Austin, Tex.

Creel, a software salesman, was diagnosed with kidney cancer in January, 2003—a few weeks after he turned 40 and a few weeks before he learned that his wife was pregnant with their first child. Creel's tumor was the size of a fist, and he was at high risk of the cancer recurring after surgery. He joined the trial in June and got biweekly Oncophage injections for a year. "There were literally no side effects. I would have the treatment and then play tennis," says Creel. He now has two children, aged 4 and 1, and has been cancer-free for five years. "I feel very, very fortunate," he says.

It took five years for Antigenics to complete the study; then came the bad news. In March, 2006, the company had to eliminate 124 patients from the trial because they didn't meet the criteria, a common occurrence in phase III trials and one that can render the final results less definitive. In the remaining participants, the vaccine worked only slightly better than standard therapy, a success rate well short of the FDA's requirements. Antigenics' stock plunged on the news.

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