Data from a Phase III trial in end-stage prostate cancer patients indicate Dendreon Corp.'s Provenge therapy is highly effective in a large group of men, company officials said.
The Seattle-based company said it narrowly missed the primary endpoint, time to objective disease progression, in a four-week trial (known as D9901) of Provenge in metastatic, hormone-resistant prostate cancer patients.
However, Christopher Henney, Dendreon's CEO, told BioWorld Today that the 127-patient trial revealed that Provenge works well in men with a Gleason score (measure of the aggressiveness of a tumor) of 7 or less. Dendreon said 75 percent of hormone-resistant patients have a Gleason score of 7 or less.
Dendreon's stock (NASDAQ:DNDN) closed Friday at $2.90, up 90 cents or 45 percent.
"What's important here is that we've identified a group of men who will benefit from Provenge therapy, but we've also identified a group who will not benefit," Henney said. "So any patient who gets a Gleason score of 8 or higher knows right away that he is not eligible for help with this."
Study D9901, believed by Dendreon to be the first randomized, double-blind, placebo-controlled Phase III trial of a cancer vaccine, treated 82 of its 127 participants with Provenge. Patients were randomized to receive three vaccinations of Provenge or placebo over four weeks.
The Provenge group showed a clinical benefit (p=0.085) that approached, but did not achieve, the prespecified primary endpoint of p=0.05, Henney said.
But in patients with a Gleason score of 7 or less, the placebo group had a median time to disease progression of nine weeks compared to 16 weeks in the Provenge-treated group, with a highly significant "p" value of 0.002 and a treatment effect of 78 percent, he said. Also, Provenge patients whose disease had not progressed six months after randomization had a greater than eightfold advantage in progression-free survival compared to those patients who received placebo (34.7 percent vs. 4 percent).
"We now have a lot of insight into how to use this drug prospectively," Henney said.
Dendreon has had a little trouble with Provenge in the past.
In January the company's stock fell 38 percent to close at $5 on news that an interim analysis of D9901 looked disappointing.
At that time, Henney cautioned that that the analysis was "inconclusive and ambiguous." (See BioWorld Today, Jan. 14, 2002.)
And seven months later, with final data in hand, he says it all makes sense.
But in between release of the interim data and Friday's announcement, another issue cropped up. Back in May, the FDA directed Dendreon to stop enrolling patients in a second Phase III study (D9902) due to questions related to product characterization. (See BioWorld Today, May 2, 2002.)
"The results we reported today are the last piece of information that we need to complete our response to the agency on that partial clinical hold," David Ural, Dendreon's president and chief science officer, told BioWorld Today. "In light of today's results, we might be looking at modifying D9902 to best make use of the information that we've learned."
Henney said any decision regarding a timeline for filing a regulatory application would come after discussions with the FDA.
Provenge is designed to jump-start the immune system by relying on the individual patient's dendritic cells to stimulate an immune reaction to cancer.
Dendreon and the pharmaceutical division of Tokyo-based Kirin Brewery Co. Ltd. have a licensing and development agreement for Provenge, giving Kirin rights and options to the Asian marketplace, with Dendreon retaining rights in North America and Europe. Signed in 1998, the deal was expanded last summer, triggering a $10 million payment to Dendreon. (See BioWorld Today, Aug. 13, 2001.)
Dendreon also is working on Mylovenge, a treatment for multiple myeloma, currently in three Phase II studies, and APC8024, a vaccine in Phase I trials designed to trigger T-cell immunity of the antigen Her2-neu for women with breast cancer.