BEERSE, Belgium, June 2, 2012 /PRNewswire/ --

Note: Data in this release correspond to ASCO Abstract LBA 4518.

Phase III Results Show Significant Improvement in Radiographic Progression-Free Survival and a Trend for Increased Overall Survival in Patients Receiving

ZYTIGA Plus Prednisone

Results observed from pre-specified interim analyses of the randomised, placebo-controlled Phase III study, COU-AA-302, demonstrated that patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (ZYTIGA(R)) plus prednisone showed a statistically significant improvement in radiographic progression-free survival (rPFS) and all secondary endpoints compared to patients treated with placebo plus prednisone. The results, announced today by Janssen, also showed a trend for increased median overall survival (OS), the co-primary endpoint, in patients receiving ZYTIGA plus prednisone. The study included 1,088 asymptomatic or mildly symptomatic patients with mCRPC who had not received chemotherapy.

This is the first randomised study to demonstrate a radiographic progression-free survival benefit and an overall survival trend in this patient population. The COU-AA-302 results are being presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO).

"Prostate cancer, the commonest cancer in men and the second commonest killer from cancer in men, is devastating for the men diagnosed with the disease and their loved ones," said Johann S. de Bono, M.D., F.R.C.P., M.Sc., Ph.D., The Institute for Cancer Research, The Royal Marsden NHS Foundation Trust, and a COU-AA-302 investigator. "These results are important since they show that metastatic castration-resistant prostate cancer patients who have not received prior chemotherapy may benefit from this agent."

The data demonstrate a statistically significant improvement in rPFS in the abiraterone acetate plus prednisone arm (ZYTIGA arm) of the study compared to the placebo plus prednisone (control) arm. The median rPFS in the control arm was 8.3 months but had not yet been reached in the ZYTIGA arm because progression events were occurring more slowly in the ZYTIGA arm compared to the control arm (N=150 vs. 251, respectively). The Hazard Ratio (HR) equaled 0.43, there was a 95% confidence interval (CI): [0.35, 0.52], and the p value was <0.0001.

Additionally, treatment with ZYTIGA plus prednisone resulted in an estimated 33 percent improvement in survival (median overall survival in the ZYTIGA arm was not reached and was 27.2 months in the control arm; HR=0.75; 95% CI: [0.61, 0.93], p=0.0097). At the time of these interim analyses, the pre-specified p-value of 0.0008 to achieve statistical significance was not reached.

Secondary Endpoints

Treatment with ZYTIGA plus prednisone also suggested significant improvements in secondary study endpoints compared to the control arm, specifically, longer time until:

- Median time to opiate use for cancer pain: the median time in the ZYTIGA arm was not reached and was 23.7 months in the control arm (HR=0.69; 95% CI: [0.57, 0.83]; p=0.0001). - Median time to initiation of cytotoxic chemotherapy for prostate cancer: 25.2 months for the ZYTIGA arm vs. 16.8 months for the control arm (HR=0.58 [95% CI: 0.49, 0.69]; p<0.0001). - Median time to deterioration in performance status: 12.3 months for the ZYTIGA arm vs. 10.9 months for the control arm (HR=0.82; 95% CI: [0.71, 0.94]; p=0.0053) for an increase in the Eastern Cooperative Oncology Group (ECOG) performance score of one point or more. The ECOG performance score is a standard measure used to assess functional status of a patient and is often used to determine prognosis and appropriate treatment. - Median time to PSA progression: 11.1 months for the ZYTIGA arm vs. 5.6 months for the control arm (HR=0.49; 95% CI: [0.42, 0.57], p<0.0001), based on The Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.

Safety Findings

Patients in the ZYTIGA arm of the study experienced more grade 3 and grade 4 adverse events than those in the control arm, including cardiac disorders (6% vs. 3%) and hypertension (4% vs. 3%), as well as increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (5.4% vs. 0.8% and 3.0% vs. 0.9%, respectively). Fatigue was the most common adverse event observed in the study.

Based on these results, Janssen plans to submit marketing applications with regulatory authorities to extend the use of ZYTIGA in men with mCRPC who have not received chemotherapy, beginning in the second half of 2012.

"These results further suggest evidence of the important clinical benefit of ZYTIGA for men with metastatic castration-resistant prostate cancer," said William N. Hait, M.D., Ph.D., Global Head, Janssen Research & Development, LLC and Head, Oncology Therapeutic Area. "The COU-AA-302 study expands our understanding of the utility of treating this disease with ZYTIGA, and is central to our goal of developing extraordinary oncology therapeutic solutions that can have a positive effect on patients' lives."

Janssen Research & Development, LLC previously announced that an Independent Data Monitoring Committee (IDMC) unanimously recommended unblinding this Phase III study after planned interim analyses found a statistically significant difference in rPFS and a trend in the difference in OS. Based on these results, the IDMC also recommended that patients in the control arm be offered treatment with abiraterone acetate.

Study Design

Study COU-AA-302 is an international, randomised, double-blind, placebo controlled Phase III study that included 1,088 men with mCRPC who had not received prior chemotherapy, who were randomised to receive abiraterone acetate (ZYTIGA) 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 are rPFS and OS.