Janssen reports Phase 3 COU-AA-302 trial results of ZYTIGA

The Janssen Research & Development, LLC ("Janssen")-sponsored registration study demonstrated a 19 percent reduction in risk of death in this study population (median OS, 34.7 vs 30.3 months, respectively; HR= 0.81 [95% CI, 0.70-0.93]; p = 0.0033), after a median follow-up of more than four years (49.2 months).1

The final analysis presented today at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain, is the first to demonstrate a statistically significant improvement in OS in this study. "OS is particularly noteworthy in COU-AA-302, because 67 percent of men in the ZYTIGA plus prednisone arm and 80 percent in the control arm received subsequent therapy. This includes 44 percent of men in the control arm who subsequently received ZYTIGA plus prednisone," said Charles Ryan, M.D., Professor of Clinical Medicine, Urology at the University of California, San Francisco, and lead investigator of the COU-AA-302 study.

"The use of subsequent therapies did not impact the statistical significance between the ZYTIGA and control arms – and makes these results all the more compelling after adjusting for the crossover effect."

The European Commission, U.S. Food and Drug Administration and regulatory authorities across the globe based approvals of ZYTIGA plus prednisone for treatment of men with mCRPC prior to chemotherapy, on a planned second interim analysis of COU-AA-302, which met the co-primary endpoint of radiographic progression-free survival (rPFS).

Based on results from the final analysis, Janssen has initiated regulatory submissions to relevant health authorities for a revision to the ZYTIGA label.

"Since the first report of interim data, ZYTIGA has become a key part of the treatment arsenal that doctors use to treat mCRPC, because it significantly delayed the progression of the disease and prolonged overall survival," said Charles Ryan.

"This final analysis also demonstrates a consistent safety profile with long-term co-administration of prednisone."

In addition, the final analysis demonstrated a significant improvement in median time to opiate use for cancer-related pain compared to placebo plus prednisone (median 33.4 vs 23.4 months, respectively; HR= 0.72 [95% CI, 0.61-0.85]; p = 0.0001).

With two additional years (a total of four years) of follow-up since the last clinical cut-off (median 49.2 months), the safety profile of ZYTIGA remained unchanged compared to previous reports.

COU-AA-302 is an international, randomised, double-blind, placebo controlled Phase 3 study that included 1,088 men with mCRPC who had not received prior chemotherapy and were randomised to receive ZYTIGA (abiraterone acetate) 1,000 milligrams (mg) administered orally once-daily plus prednisone 5 mg administered twice-daily or placebo plus prednisone 5 mg administered twice-daily.

The co-primary endpoints of the study were rPFS and OS. Key secondary endpoints included time to opiate use, time to initiation of chemotherapy, time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration and time to prostate-specific antigen (PSA) progression.

"The treatment paradigm for prostate cancer has significantly evolved over the last few years, primarily as a result of a deeper understanding of the disease that has led to the development of treatment options beyond chemotherapy," said Jane Griffiths, Company Group Chairman, Janssen Europe, the Middle East and Africa (EMEA).

"Janssen is proud to be leading the way in innovation in this area and today’s announcement reinforces the company’s commitment to continued research to improve the lives of men with prostate cancer."