Dendreon Corp. intends to amend the protocol for a Phase III trial of Provenge, a prostate cancer drug, to enroll only advanced hormone-resistant prostate cancer patients with a Gleason score of 7 or less.
The trial in question, known as D9902, was initiated earlier, but now will enroll 225 men over the next 12 to 14 months in order to study time to disease progression as well as the time to onset of disease-related pain.
Analysis from D9902 will be combined with a previous Phase III trial, referred to as D9901, and submitted for regulatory approval, possibly by the end of 2004.
Study D9901 is key to Dendreon's regulatory process, since the trial taught the Seattle-based company that its product works best in men who have a Gleason score (measure of the aggressiveness of a tumor) of 7 or less. (See BioWorld Today, Aug. 12, 2002.)
"To know in advance the population that will respond to a drug is a tremendous advantage for drug development and marketing," David Urdal, Dendreon's president and chief scientific officer, told BioWorld Today.
A Gleason score of 7 or less is associated with a less aggressive form of prostate cancer, yet is present in 75 percent of the target population, Urdal said.
Study D9902 is just resuming, following a delay that began in May when the FDA halted enrollment pending submission of information referencing the manufacture and characterization of Provenge. (See BioWorld Today, May 2, 2002.)
At the time of the delay, about 100 men had enrolled and they were permitted to continue with the trial. Urdal said data from those patients would be included in the regulatory package as part of the safety analysis.
In late October, Dendreon apparently satisfied the FDA's concerns related to D9902 and was given clearance to resume the study. The resumed study will now focus on just the Gleason 7 men. (See BioWorld Today, Oct. 29, 2002.)
Provenge uses a recombinant antigen derived from prostatic acid phosphatase that is combined with a patient's own dendritic cells and reinfused into the patient to stimulate an immune response. Dendreon has high hopes for Provenge, given its performance in D9901, a 127-patient, four-week trial that barely missed its endpoint of time to objective disease progression in metastatic, hormone-resistant prostate cancer patients.
However, the placebo group of patients with a Gleason score of 7 or less demonstrated a median time to disease progression of nine weeks, compared to 16 weeks for the Provenge-treated group, with a "p" value of 0.002 and a treatment effect of 78 percent, the company said.
Provenge patients whose disease had not progressed six months after randomization had a greater than eightfold advantage in progression-free survival, compared to patients who received placebo (34.7 percent vs. 4 percent).
Dendreon said Provenge was well tolerated, with the most common side effects being chills and fever, which were most often infusion-related and temporary.
Dendreon's stock (NASDAQ:DNDN) rose 70 cents Thursday, or 17.5 percent, to close at $4.70.