Senior Staff Writer

Boosting hopes for a wider label than previously thought, Dendreon Corp. released final three-year follow-up data from a Phase III study of Provenge.

The latest findings from the trial, called D9901, showed a statistically significant survival benefit in all Provenge-treated advanced prostate cancer patients. That bolsters initial data from the study, reported two years ago, which showed a non-statistically significant 43 percent clinical benefit in delaying time to disease progression compared to placebo and delayed the onset of disease-related pain in men with androgen-independent prostate cancer whose cancer had a Gleason score of 7 or less. (See BioWorld Today, Aug. 12, 2002.)

"In patients with Gleason scores of 7 or below, which is about 75 percent of men with late-stage prostate cancer, we had shown a pretty dramatic benefit," President and CEO Mitchell Gold told BioWorld Today. "So based on that data that we got back then, we started another pivotal Phase III study that obviously was looking at patients that had the biggest benefit - those with a Gleason score of 7 or below - knowing that we wouldn't get the final survival data from that first study until right now."

Investors immediately took to the news, driving up Dendreon's stock by 23.9 percent. Its shares (NASDAQ:DNDN) gained $1.90 Thursday to close at $9.85.

The data stem from a pre-specified, 36-month survival analysis of the double-blinded, placebo-controlled study. It tested the investigational immunotherapy in 127 patients with asymptomatic, metastatic androgen-independent prostate cancer and found a survival benefit in the overall intent-to-treat patient population, defined as all patients randomized in the study regardless of their Gleason score.

"Now we can go after 100 percent of the market," Gold said. "And obviously, survival is a much better endpoint than progression. We're still digesting the news, and certainly it's pretty exciting at the company, but I think it's creating in the clinical community's eyes a fundamental change in the way they're thinking about treating cancer. It's really going to be a paradigm shift in the way that cancer specialists think about using products like Provenge in the clinical setting."

The survival benefit is greater than that observed with any type of treatment in any published Phase III study in late-stage prostate cancer, the company noted. Earlier this year, Seattle-based Dendreon released data showing that patients receiving Provenge had an 89 percent overall increase in survival time compared to placebo.

The company did not release specific numbers from its latest analysis, as the study's principal investigators plan to submit the complete data for presentation at an upcoming scientific meeting and for publication in a peer-reviewed medical journal.

But also among the data were findings that showed the percentage of patients alive in the Provenge-treated group at 36 months to be substantially greater than the percentage of patients who received placebo. The final data also showed a statistically significant survival benefit in the group of patients with Gleason scores of 7 and less. Provenge was well tolerated, with the most common adverse events reported being fever and chills lasting for one to two days.

The company said it has the wherewithal and means to internally push the product into the U.S. market. Earlier this year, it raised $130.7 million through a public offering to develop a commercial infrastructure for Provenge. (See BioWorld Today, Jan. 23, 2004.)

"We've always had a desire, in our partnering discussions, to play a major role in the commercialization of Provenge in the U.S. market," Gold said. "Today's data only strengthen that belief. There's certainly no reason why Dendreon, given its resources, can't commercialize Provenge on its own in the U.S. And if a partner wants to get a share of the U.S. profits, they're going to have to bring a lot to the table."

He said it "makes sense" for the company to consider partners in Europe and Asia.

Dendreon has begun sharing its latest findings with the FDA to determine the data's role in an eventual new drug application. Gold said the regulatory strategy could be more efficient as a result, and envisions an approval sometime in 2006.

The product is being evaluated in a pivotal Phase III trial called D9902B. The double-blind, placebo-controlled study is operating under a special protocol assessment agreement with the FDA, which has designated Provenge a fast-track product, and is enrolling 275 men at 70 sites across the U.S.

Gold declined to forecast the study's completion date, but after beginning in 2002 it was amended, as Gold mentioned, to enroll only advanced hormone-resistant prostate cancer patients with a Gleason score of 7 or less. (See BioWorld Today, Dec. 6, 2002.)

"The bigger-picture news for the company, with the Provenge data, is that it really validates our cancer immunotherapy platform," Gold said, adding that another product based on the Antigen Delivery Cassette technology is APC8024. "That's another cancer immunotherapy that targets HER-2/neu for breast cancer patients. It's finished Phase I studies, and we're now about to embark on a large Phase II study."

Dendreon also has produced multiple monoclonal antibody product candidates for oncology. And separate from that program, a cancer collaboration with South San Francisco-based Genentech Inc. is focused on small-molecule inhibitors and monoclonal antibodies for a calcium channel gene called Trp-p8.