Promising Test for Dendreon’s Prostate Cancer Drug

April 15, 2009 By ANDREW POLLACK <> A prostate cancer <>  drug developed by the Seattle biotechnology company Dendreon <>  prolonged the lives of men in a decisive clinical trial, the company announced Tuesday morning.

The widely anticipated results could pave the way for the drug, called Provenge, to become the first so-called therapeutic cancer   “vaccine” to win approval in the United States after numerous failures of such drugs. “This looks like a proof of concept that cancer vaccines can and do work,” said Jeffrey Schlom, an expert on the vaccines at the National Cancer Institute <> . Such vaccines work by harnessing the patient’s own immune system to fight the cancer. But the success in the trial could revive complaints about the Food and Drug Administration <> , which two years declined to approve Provenge despite an endorsement by one of the agency’s advisory committees.

The F.D.A. instead said it wanted more proof that the drug worked and would await results from a trial that was then underway, whose results were announced Tuesday.

The F.D.A.’s decision two years ago ignited an outcry from some prostate cancer patients and from investors in Dendreon, who said the agency was being unreasonable and denying patients a treatment that might work. Tensions ran so high at one point that two prostate cancer specialists, who had urged the F.D.A. not to approve the drug, attended a major conference accompanied by bodyguards, saying they had been threatened.

“Since that delay we have lost a lot of good men,” Ted Girgus of Bellingham, Wash., who has advanced prostate cancer, said Tuesday, calling the F.D.A. decision “a punch in the stomach.” Mr. Girgus, 65, who also owns Dendreon stock, said patients like himself are “looking into the abyss.”

“We know what our prognosis is,” he said. “But we want a chance.”

Dendreon did not reveal the actual results of its trial, saying they would be presented at a urology meeting on April 28.

But Mitchell Gold, the company’s chief executive, told analysts on a conference call, “It was an unambiguous hit on the primary endpoint of overall survival.” He said the outcome met the goals the company and the F.D.A. had agreed upon and that the results were consistent with those seen in earlier trials of Provenge.

In an interview Dr. Gold said Provenge would have had to reduce the risk of death by 22 percent compared to a placebo to meet the F.D.A. requirements for statistical significance.

Dendreon’s stock soared on the news. The shares were up more than 130 percent for the day, closing at $16.99.

The stock, which closed Monday at $7.30, had nearly tripled from its 52-week low of $2.55 in early March on anticipation of positive results. But there were also many investors who shorted the stock, betting the drug would fail in the clinical trial.

The trial involved 512 patients whose cancer had spread beyond the prostate gland and who were no longer benefiting from therapies intended to deprive the tumors <>  of testosterone <> .

Dr. Gold said there were about 100,000 men who get such a diagnosis each year. The only approved treatment for them now is the Sanofi-Aventis <>  chemotherapy <>  drug Taxotere, which extended median survival by about 3 months in trials.

Mark Monane, an analyst at Needham & Company, said sales of Provenge might reach $500 million to $1 billion a year.

Therapeutic vaccines like Provenge do not aim to prevent the disease, as a childhood vaccine does. Rather they aim to train the body’s immune system to attack the cancer once the patient is already ill.

There is already an approved treatment for bladder cancer <>  that stimulates the immune system in general, but not specifically to fight the cancer. The cervical cancer vaccine <>  now in use, Gardasil, is a more traditional preventive vaccine that works because cervical cancer <>  is caused by a virus.

Proponents say cancer vaccines, also known as immunotherapy, could be a more precise way to attack cancer than bombarding them with poisons, as is now down in chemotherapy.

But development of cancer vaccines has been a path marked by numerous failures until now. Indeed, another prostate cancer vaccine called GVAX, developed by Cell Genesys <> , failed in late-stage clinical trials last year.

Provenge had become a symbol of the sometimes passionate debate between patients who want faster access to experimental drugs and those who believe society as a whole benefits from greater proof that drugs work.

In an earlier trial, men who received Provenge lived a median of 25.9 months, compared with 21.4 months for those who received a placebo. At the end of three years, 34 percent of the men who got Provenge were alive, compared to only 11 percent for those who received a placebo.

Based on those results, an advisory panel to the F.D.A., meeting in March 2007, voted 13 to 4 that there was “substantial evidence” that the drug worked, and 17-0 that the drug was safe.

Still, some members of the committee said the evidence was somewhat weak because that trial involved only 127 men. And it had been intended to measure something different — not whether Provenge prolonged life, but whether it delayed the worsening of cancer. And the drug failed to do that by a statistically significant measure.

Two months later, the F.D.A. declined to approve Provenge, saying that more data were needed.

Protestors rallied outside an F.D.A. office in Rockville, Md., in September 2007. They took out ads in newspapers and on buses in the Washington area, including one that said “The FDA: killing hope, shortening lives.”

A group called Care to Live sued the F.D.A. to try to reverse the decision. But the courts essentially threw out the lawsuit, saying the F.D.A. had not made a final decision that could be challenged.

Harsh criticism was also directed against two prostate cancer specialists who had voted against Provenge on the advisory committee and later wrote letters to the F.D.A. urging that the drug not be approved. The two doctors, Howard I. Scher of Memorial Sloan-Kettering Cancer Center <>  and Maha Hussain of the University of Michigan <> , were accompanied by bodyguards when they attended the nation’s largest cancer medical meeting in 2007.

Still, many prostate cancer patient advocacy groups did not support all those tactics or the lawsuit.

“I think the stockholders were more angry than the prostate cancer community,” said Jim O’Hara, a prostate cancer survivor and help line facilitator for the Prostate Cancer Research Institute, a patient education group. “The majority of the community that I talk to wants to see something approved that has gone through legitimate tests.”

Since the F.D.A. declined to approve Provenge, prostate cancer drugs from Cell Genesys, Novacea <>  and GPC Biotech have failed in clinical trials.

Patients treated with Provenge have some white blood cells removed. Dendreon mixes those white cells, which are part of the immune system, with a genetically engineered protein that is a combination of an immune system stimulator and a molecule found in prostate cancer cells but only rarely elsewhere in the body.

The cells are then infused back into the patient, where they are meant to stimulate the immune system to attack anything that looks like the telltale prostate cancer molecule.

The treatment requires three infusions spaced two weeks apart, rather than periodic infusions over the course of months, as is common with chemotherapy. Provenge’s side effects also appear to be milder than those of Taxotere, some doctors say.

“Compared to standard chemotherapy, it’s just a whole lot easier for patients,” said Dr. David Penson, associate professor of urology at the University of Southern California <> . He was an investigator in the trial and was a consultant to Dendreon a few years ago.