Bavarian Nordic A/S today announced that they have received a letter of concurrence from the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for a Phase 3 study required for product registration for its product candidate, PROSTVAC®, for the treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (sound familiar, these are the same criteria as the Provenge approval). This agreement means that the Phase 3 study can proceed.
According to Anders Hedegaard, President & CEO of Bavarian Nordic the trial could start in the late summer of 2011.
About the Anticipated Phase 3 Trial
The Phase 3 program will include a single global, strongly powered, randomized, double-blind, placebo-controlled study that is expected to enroll about 1,200 men in three study arms. Men in the two active study arms will receive either PROSTVAC® alone or PROSTVAC with adjuvant doses of GM-CSF (which was included in Phase 2).
Men who have metastatic disease and have failed hormone therapy, but who have not yet received other treatment options such as chemotherapy, will be eligible to enroll in the study. The primary endpoint is overall survival (OS). For the study outcome to be positive, either one or both of the treatment arms must be superior to placebo. The phase 3 trial is sized so that each comparison requires 534 deaths with sensitivity for estimated death hazard ratios of 0.82 or less.
About Special Protocol Assessments
The Special Protocol Assessment (SPA) process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a Biologics License Application or New Drug Application (BLA, NDA). Final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the Phase 3 trial.
PROSTVAC® is an “off-the-shelf” therapeutic vaccine as opposed to the already approved provenge vaccine that is individualized. In April 2010, PROSTVAC® was granted Fast Track designation by the FDA for the treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).
In a prospective randomized, double-blind, placebo-controlled Phase 2 study of 125 patients with metastatic prostate cancer, men in the PROSTVAC® group had a significantly longer median overall survival by 8.5 months compared to the control group (p=0.006). The hazard ratio estimate for overall survival from the study is 0.56 (95% CI 0.37-0.85).
Joel T Nowak, M.A., M.S.W.