A month after reporting a miss in a Phase III trial of its prostate cancer drug Provenge, Dendreon Corp. rebounded with data from the study showing a statistical improvement in patient survival rate.

Results of the Phase III trial, study D9901, indicated that patients receiving Provenge had a four and a half month improvement in median survival, and a greater than threefold increase in survival at 36 months vs. patients receiving placebo. Dendreon President and CEO Mitch Gold called the results "the largest survival benefit seen in late-stage prostate cancer."

Prior to the Provenge study, the longest survival rate had been reported with Taxotere (Sanofi-Aventis Group) at two and a half months, he said.

Dendreon's stock (NASDAQ:DNDN), which had gained $1.07 Wednesday, fell 16 cents Thursday to close at $7.89.

According to D9901 study results, patients receiving Provenge had a median survival of 25.9 months, compared to 21.4 months for patients receiving placebo. At the end of three years, about 34 percent of the Provenge patients remained alive vs. 11 percent in the placebo arm.

"I think this is the most encouraging piece of information we have received on Provenge to date," Gold said of the trial results, which also indicated that the drug produced few side effects.

That is good news for Provenge, which has had trouble meeting primary endpoints that show a statistically significant delay in time to disease progression.

Results from the D9901 trial reported in August 2002 showed that the drug narrowly missed that endpoint. Data from a companion Phase III study, D9902A, released last month, also reported a miss, causing Dendreon's stock to drop more than 26 percent on Jan. 11 to close at $7.62. (See BioWorld Today, Jan. 12, 2005.)

However, Gold said progression "probably isn't the most appropriate endpoint for cancer immunotherapies."

"It takes about nine to 11 weeks for progression to occur, but we know it takes about eight weeks for immunotherapies to fully kick in," he said. "So it's difficult to impact the progression endpoint."

Patient survival is another matter. With statistical improvement reported from the D9901 trial, Dendreon now awaits survival results from its D9902A trial, expected during the second half of the year. The company said preliminary analysis of the D9902A trial suggests a similar trend in survival to the D9901 study.

"As long as the data are supportive, I believe those two data sets combined could form the basis of our [biologics license application] for potential approval of Provenge," Gold told BioWorld Today.

Dendreon is enrolling patients in a third Phase III trial, D9902B, which could function as an approval study or post-approval study, depending on the D9902A results.

When asked about concerns raised last month regarding Provenge's future, Gold said Thursday's data show that "Provenge is clearly having a benefit on patients," and "hopefully, any skepticism there is relieved right now."

He added that progression benefit likely is a difficult endpoint for any immunotherapy to meet, "but longer-term endpoints like survival, which are clearly the gold standard in cancer studies, are endpoints that we are impacting."

Provenge is designed to stimulate the immune system to attack cells that express prostatic acid phosphatase (PAP), a protein found on about 95 percent of prostate cancer cells. Dendreon uses its Antigen Delivery Cassette technology to deliver small pieces of the PAP protein to antigen-presenting cells, which activate other cells in the immune system to destroy the cancer cells.

Final data from the D9901 study will be presented by Eric Small, professor of medicine and urology at the University of California in San Francisco, during the 2005 Multidisciplinary Prostate Cancer Symposium in Orlando, Fla., Saturday.

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