Dendreon Corporation said the US Food and Drug Administration (FDA) has agreed to an amended Special Protocol Assessment (SPA) for the phase III IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment, also known as D9902B) clinical trial of Provenge (sipuleucel-T), the company's investigational active cellular immunotherapy for the treatment of advanced prostate cancer.
In addition, the FDA has reconfirmed that they would accept a positive interim or final analysis from the IMPACT trial to amend the Biologics License Application (BLA) for licensure of Provenge.
The amended SPA accelerates the expected timing of the final IMPACT results by approximately one year while maintaining comparable powering of the study's interim and final results. By increasing the number of events and decreasing the alpha (false positive error) spending function for the interim analysis, the company is able to reduce the number of events for the final analysis (from 360 to 304) and still maintain a comparable statistical power for both the interim and final analyses. Interim results are still expected in the second half of 2008; however, final results are now expected in the second half of 2009 rather than 2010.
Based on the statistical plan in the amended SPA, if the treatment effect at the interim analysis for the IMPACT trial is consistent with the integrated results of the previous two completed phase III studies (D9901 and D9902A), Dendreon would expect to achieve the pre-specified criterion for significance and would amend the BLA submission with the FDA based on these interim results.
"The amendment of the SPA allows us to accelerate the expected timing of our final results by a year while maintaining comparable power for the study," said Mitchell H. Gold, president and chief executive officer, Dendreon. "Our commitment to helping patients with prostate cancer is unwavering, and we remain focused on providing the necessary data to the FDA as quickly as possible to enable us to bring PROVENGE to the men in need of a new treatment option."
The IMPACT trial is a randomised, double blind, placebo controlled Phase 3 study, which enrolled just over 500 men with metastatic, androgen independent prostate cancer with a primary endpoint of overall survival.
Provenge may represent the first product in a new class of active cellular immunotherapies (ACIs) that are uniquely designed to use live human cells to engage the patient's own immune system with the goal of eliciting a specific long-lasting response against cancer. In clinical studies, patients typically received three doses of Provenge over a one-month period as a complete course of therapy.