Prostate Cancer Vaccine Shows Promise in a Trial

An experimental treatment tripled the survival rate of men with advanced prostate cancer in a clinical trial, doctors said yesterday, a result they said represents perhaps the first significant success for therapies known as cancer vaccines.

The treatment, developed by Dendreon, a Seattle biotechnology company, is called a vaccine not because it prevents disease but because it tries to harness the body's own immune system to fight cancer after the disease has developed. Many such cancer vaccines have failed in clinical trials and none have reached the market in the United States.

But Dendreon's treatment, called Provenge, now seems to have a shot at becoming the first to win approval from the Food and Drug Administration, especially if another trial expected to be completed by the end of the year confirms the results.

In a final-stage clinical trial involving 127 men with advanced prostate cancer, 34 percent of those who received Provenge were alive after three years, compared with 11 percent of those who took a placebo. The median survival, meaning the time by which half the patients had died, was 25.9 months for those who received Provenge, compared with 21.4 months for those who took the placebo.

"This study has shown a survival advantage to using this drug in patients with very limited options," said Eric J. Small, the lead investigator in the trial and a professor of medicine at the University of California, San Francisco. "It really gives people hope for the future."

The 4.5-month increase in survival that was achieved by Provenge is greater than the roughly 2.5-month benefit shown in clinical trials of Taxotere, a drug from Sanofi-Aventis. Taxotere is the only approved chemotherapy for patients, like those in the Provenge trial, whose cancer has spread beyond the prostate gland and is no longer being controlled by hormonal therapy.

Philip Kantoff, a researcher not involved with the trial, called the new results "very interesting, provocative, promising," but "certainly not definitive." Dr. Kantoff, chief of solid tumor oncology at the Dana-Farber Cancer Institute in Boston, said the difference in survival was "a lot in such a small study; it just makes one skeptical."

The trial results are scheduled to be presented Saturday at a prostate cancer symposium in Orlando, Fla., organized by three medical societies and the Prostate Cancer Foundation. Dendreon, which sponsored the trial, announced in October that the drug had prolonged lives, but the actual statistics will be revealed for the first time at the symposium.

Dendreon's stock rose $1.08, or more than 15 percent, yesterday, closing at $8.05, even though the results were not officially released until last night. Provenge could be the company's first product on the market.

The main goal of the Provenge trial was to see if the drug delayed the worsening of cancer, a measure known as time to progression. Dendreon had previously announced that the drug failed to do that by a statistically significant amount, though the company said the drug did delay progression in patients with less aggressive cancer.

But Dr. Small, who said that he had no financial relationship with Dendreon, said that the time to progression was probably not the right measure to use for cancer vaccines because cancer can worsen before the immune system starts to fight it. He said Provenge improved survival for all patients, not just those with less aggressive cancers.

Dr. Small said the treatment was much less toxic than chemotherapy, with the main side effects being flu-like symptoms that last a short time.

In the treatment, patients have their blood run through a machine for two or three hours to extract certain immune system cells. The cells are then mixed with a protein called prostatic acid phosphatase that is present on most prostate tumors. The mixture is then given back to the patient in a one-hour infusion. The process is repeated three times over the course of a single month. The idea is to alert the immune system that cells containing prostatic acid phosphatase, namely tumor cells, are something to be attacked like a germ.

Prostate cancer is one of the most common cancers. There are about 230,000 new cases diagnosed and 30,000 deaths in the United States each year.

04.14.09, 12:31 PM EDT

A victory for the company’s controversial prostate cancer treatment, but more debate lies ahead.

Shares in tiny biotech Dendreon tripled early Tuesday to almost $21 after the company said its prostate cancer treatment Provenge extended survival in a 500-patient clinical trial.

Although details are sparse and significant questions about Provenge remain, the result is a major victory for Dendreon ( DNDN - news - people ), and for researchers working on treatments that aim to fight cancer using patients’ own immune systems. Two years ago, Provenge was rejected by the Food and Drug Administration, causing shares in the company to plummet. It could take a year for the FDA to reach a new decision on Provenge.

“It certainly sounds good, but we really need to see the details,” says Otis Brawley, chief medical officer of the American Cancer Society. “I will be watching with interest and some hope.”

Twenty-nine thousand men die annually from prostate cancer, but there are few treatments once the disease has spread to the bone. The only approved option is Taxotere, a chemotherapy made by Sanofi-Aventis ( SNY - news - people ) that can cause hair loss, fatigue and fluid retention. Provenge might give patients a new option, although it will cost them and their health plans—Dendreon Chief Executive Mitchell Gold said on a conference call Tuesday morning that the price would be “similar” to other biotech cancer drugs, which can run $50,000 per patient.

If approved, “this would represent an important proof of principle that individualized immune therapies ... can help patients with common cancers, says William K. Oh, director of Genitourinary Oncology at the Dana-Farber Cancer Institute. “That would be a major breakthrough.”

One big question, he says, is how Provenge might be working. If it doesn’t slow the progression of the disease, “what exactly is happening to keep the patients alive?” Dr. Oh asks.

Also, the complexity of the Provenge treatment procedure could limit its use. “It is labor intensive and is probably not the best for someone who is elderly and frail,” says Dr. Lech Dabrowski of Maimonides Medical Centerin Brooklyn.

Provenge aims to remove some of a patient’s immune cells, treat them and replace them in order to spur the immune system to attack the tumor. In two previous studies, it failed to slow the growth of tumors, but a later analysis showed that the drug appeared to be extending patients’ lives anyway.

Now doctors (and investors) will be waiting to see how well the full Provenge data answers questions that were previously asked about the drug. Although Seattle-based Dendreon announced that the 500-person study succeeded, it said it is holding details for the annual meeting of the American Urological Association in two weeks.

If the results are verified, it would be the first time a cancer vaccine has clearly improved survival in a large-scale trial after many failures. “The immunotherapy space has seen countless failures, and Dendreon’s data should reinvigorate the space,” wrote Joel Pantginis of Merriman Curhan Ford in an investor note. Pfizer ( PFE - news - people ), GlaxoSmithKline ( GSK - news - people ) and Bristol-Myers Squibb ( BMY - news - people ) have already waded into the field.

One big question for Provenge will be how statistically significant the results are—a measure of whether or not the result might be due to chance. If the result is borderline, issues like how Dendreon handled an interim analysis last year could still lead to questions. (See: Dendreon Disclosure Could Endanger Provenge Study.)

Brawley also wants to know how many months longer patients lived. He says he wants to know exactly how deaths were counted. “Surprisingly some companies often lack the expertise to fully analyze these types of trials appropriately,” he says.

Another issue that arose in previous studies was a worry that both Provenge and a sham treatment used in those studies might be increasing the risk of stroke. How many strokes occur in the 500-patient study will be another important question.

On the conference call, Gold, the Dendreon chief executive, said the results of the study were “unambiguous” even after the company tried to adjust for potential statistical issues. He said that the size of the survival benefit was comparable to what had been seen in previous studies; the previous analysis had shown a four-month median survival benefit.

There’s plenty of time for more debate. Dendreon says it will resubmit its application to sell Provenge in the fourth quarter of this year. The Food and Drug Administration will then have six months to review the new data. That means that it could be a year before the FDA makes another decision.

Because Provenge is complicated to make, investors will be watching closely for information on how much Dendreon can manufacture and how much the treatment will cost. Dendreon says it will hold an analyst meeting this summer to further discuss the results.

Daniel P. Petrylak, director of the prostate cancer program at Columbia University/New York Presbyterian Hospital, called the result “great news,” especially given the three promising prostate cancer treatments that have recently failed. He is doing research and consulting for Dendreon. “We needed some positive news,” he says. “I’m very excited about seeing the final data.”

http://www.forbes.com/2009/04/14/provenge-prostate-cancer-business-healthcare-dendreon.html?partner=yahootix

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