Reporting positive survival data from a supporting Phase III study of its prostate cancer drug, Provenge, Dendreon Corp. is preparing to meet with the FDA to discuss filing for regulatory approval.
Analysis of the three-year data from the 98-patient D9002A study showed a 20 percent improvement in median survival for patients with metastatic, androgen-independent prostate cancer who received Provenge as opposed to placebo. After 36 months, the percentage of patients alive in the Provenge-treated group was "substantially greater" than the percentage in the placebo group, said Mitchell Gold, president and CEO of Seattle-based Dendreon.
These results were not statistically significant on their own, but they confirmed data reported following an earlier trial, D9901, of Provenge in 127 patients. Results from D9902A, designed as a smaller companion study, were intended to be pooled with data from the earlier trial, Gold said.
An analysis of the combined data showed a statistically significant survival benefit of 23 percent over placebo in the 225-patient population. The company plans to report more detailed results during an upcoming medical meeting.
"Clearly, it was positive in that we're seeing a similar benefit in median survival in the second study," Gold said, adding that the entire data set "could form the basis of a BLA [biologics license application] for Provenge."
Shares of Dendreon (NASDAQ:DNDN) climbed 13 percent Thursday, up 82 cents to close at $7.02.
The company reported survival results from the first study in February, showing a four-and-a-half month, or 21 percent, improvement in median survival in patients treated with Provenge vs. placebo. Patients in the Provenge group also had a greater than three-fold increase in survival at 36 months compared to placebo. (See BioWorld Today, Feb. 18, 2005.)
"What's very reassuring to us is that we're seeing similar benefit in survival, not only in median numbers, which fall between 20 and 23 percent, but that the hazard ratio between the three data sets - D9901, D9902A and the pooled data from both - are very similar," Gold told BioWorld Today. "That gives us a very precise estimate of the true treatment effect of Provenge."
Dendreon's next move will be to compile data in a briefing document and begin discussions with the FDA to determine whether Provenge's promising survival data is sufficient for a BLA, despite the drug missing its primary endpoints of time to disease progression in both trials.
Gold, however, has maintained that disease progression represents an unrealistic endpoint for immunotherapeutics like Provenge because it "usually takes eight to 10 weeks to get the immune system going," while progression can occur in nine to 11 weeks.
Provenge, which could end up being the first cancer immunotherapy to go before the FDA for approval, is designed to stimulate the immune system to attack cells that express prostatic acid phophatase (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 cancer cells.
"We believe survival is the endpoint that's most important from a regulatory perspective and from a clinical perspective," Gold said. "Clearly [Provenge] is having an impact on patients."
The drug has been well tolerated in all human studies, with a minimum side effect profile. The most common effects are fever and chills that last for one to two days.
Dendreon expects feedback from the FDA regarding plans for a BLA submission sometime during the fourth quarter.
In the meantime, the company has a third Phase III trial, D9902B, enrolling 225 prostate cancer patients with Gleason scores of seven or below.
"That's where we initially thought the drug would have the biggest impact," Gold said, "but now we know that the survival benefit is seen across all scores."
The company has not yet determined how it will use the results of this third trial, though it could offer Dendreon a second pathway for Provenge approval, he said.
"We plan to talk with the FDA about how best to incorporate that study into our regulatory strategy," he said.