Following a six-month delay, Dendreon Corp. received FDA clearance to resume enrollment in its second Phase III trial of Provenge, a therapeutic vaccine for hormone-resistant prostate cancer patients.
The FDA forced Dendreon to suspend new enrollment of study D9902 in May pending submission of information referencing the manufacture and characterization of Provenge. However, the 100 or so patients enrolled at the time of suspension were allowed to continue. (See BioWorld Today, May 2, 2002.)
"This is a significant event for the company," David Urdal, president and chief scientific officer of Dendreon, told BioWorld Today. "Now we've got both strong clinical evidence of the potential benefit of our product, and the manufacturing and characterization of our product has been accepted by the agency, so I think we are clearly on a march forward to registration."
He said the company anticipates completing enrollment in D9902 over the next year, and expects to add another 50 patients, making a total of 150 in the study.
It's unclear when the company would file a biologics license application for Provenge.
D9902 was designed to work as the supporting trial for D9901, a four-week Phase III trial of 127 end-stage, hormone-resistant prostate cancer patients. In August, Dendreon conceded that D9901 narrowly missed its primary endpoint, time to objective disease progression. (See BioWorld Today, Aug. 12, 2002.)
Nevertheless, the study helped Dendreon differentiate between populations that could benefit from the vaccine. Company officials said 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.
In D9901, the Provenge group showed a clinical benefit (p=0.085) that approached, but did not achieve, the prespecified primary endpoint of p<0.05.
"We believe we have identified a key factor in whether a patient will respond to this drug. I can't overstate how important that knowledge is, and one of the key objectives in 9902 will be to achieve confirmation of that observation of patients with Gleason 7 or less," Urdal said. "From 9901 we also learned that that product is very well tolerated, which one would expect in an immunotherapy-type product."
In patients with a Gleason score less than or equal to 7 in study D9901, 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 treatment effect of 78 percent, according to the company.
The primary endpoint in both trials is time-to-disease progression, with a secondary endpoint of time to development of disease-related pain.
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 in August 2001, triggering a $10 million payment to Dendreon. (See BioWorld Today, Aug. 13, 2001.)
Dendreon's stock (NASDAQ:DNDN) closed Monday at $3.27, up 17 cents.