HIGH WYCOMBE, England, May 25, 2011 /PRNewswire/ --

- Findings Published Today in The New England Journal of Medicine

A study published today in The New England Journal of Medicine in patients with metastatic advanced prostate cancer following chemotherapy who were treated with abiraterone acetate plus prednisone/prednisolone showed a significant improvement in overall survival compared to patients treated with prednisone/prednisolone plus placebo. The study was sponsored by Janssen.

The randomized, placebo-controlled Phase 3 study, COU-AA-301, evaluated whether the investigational agent abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration resistant prostate cancer (CRPC) - also defined as metastatic prostate cancer - whose disease had progressed following chemotherapy.

Androgens are hormones that promote the development and maintenance of male sex characteristics.[1] However, in prostate cancer, androgens can help fuel the tumour's growth.[2] Androgen production primarily occurs in the testes and adrenal glands; in men with prostate cancer, the tumour tissue is an additional source of androgens.[3] Abiraterone acetate is an oral androgen biosynthesis inhibitor that works by selectively inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources.[4]

After a median follow-up of 12.8 months, overall survival for the group receiving abiraterone acetate plus prednisone/prednisolone was 14.8 months vs. 10.9 months for placebo plus prednisone/prednisolone (representing a 36 percent increase in median survival). Treatment with abiraterone acetate also resulted in a 35 percent reduction in the risk of death (HR=0.646; 95 percent CI: 0.543, 0.768; p<0.0001) compared with placebo. This study included 1,195 patients with metastatic CRPC who were previously treated with one or two chemotherapy regimens, at least one of which contained docetaxel.

The study investigators stated that, overall, despite the advanced age and level of frailty in the treatment population, patients had high compliance with abiraterone acetate treatment, for which the toxicities were easily manageable and reversible.[5]

"Given that men with metastatic advanced prostate cancer have few options, we are pleased with the results of this rigorous study which show that abiraterone acetate may extend survival in these patients," said Johann S. de Bono, MD, FRCP, MSc, PhD, The Institute for Cancer Research, The Royal Marsden NHS Foundation Trust, and lead author. "The data indicate that abiraterone acetate has the potential to meet a significant unmet need for advanced prostate cancer patients and their families."

Men who received abiraterone acetate and prednisone/prednisolone also showed significant improvements in secondary study endpoints when compared to the prednisone/prednisolone plus placebo group: time to PSA progression (TTPP) [median 10.2 months for abiraterone acetate vs. 6.6 months for placebo, HR=0.580 (95 percent CI: 0.462, 0.728); p<0.0001] and an increase in radiographic progression-free survival (rPFS) [median 5.6 months for abiraterone acetate vs. 3.6 months for placebo, HR=0.673 (95 percent CI: 0.585, 0.776); p<0.0001].

Total confirmed PSA response, defined as greater than or equal to a 50 percent decrease from baseline, was achieved in 29 percent of patients treated with abiraterone acetate vs. 6 percent in the prednisone/prednisolone plus placebo group [p<0.0001].

"Prostate cancer is the fifth most common cancer globally, and is the most common cancer in men in the UK," said Dr Rob Jones, Clinical Senior Lecturer in the Institute of Cancer Sciences at the University of Glasgow. "We believe the findings of this Phase 3 study of abiraterone acetate are an important development for a patient population in need of more therapeutic solutions."

Patients in the abiraterone acetate group experienced more mineralocorticoid-related adverse events than those in the prednisone/prednisolone plus placebo group. The most common adverse events were fluid retention (31 percent vs. 22 percent), hypertension (10 percent vs. 8 percent) and hypokalemia (17 percent vs. 8 percent). Grade 3/4 hypokalemia and hypertension were more frequent in the abiraterone acetate arm than in the placebo arm (3.8 percent vs. 0.8 percent and 1.3 percent vs. 0.3 percent, respectively). Liver function test abnormalities were observed in 10 percent of abiraterone acetate-treated patients compared to 8 percent in the prednisone/prednisolone plus placebo group. Cardiac disorders were observed in 13 percent of abiraterone acetate patients vs. 10 percent of patients who received placebo.

The Independent Data Monitoring Committee recommended unblinding this Phase 3 study at interim analysis, as these results exceeded the preplanned stopping criteria. Furthermore, the IDMC recommended that patients in the prednisone/prednisolone plus placebo group be offered treatment with abiraterone acetate.

The results of this randomized, double-blind, placebo-controlled study were also presented in part during a late-breaking presentation at the Presidential Symposium at the 35th Annual European Society for Medical Oncology (ESMO) Congress in Milan, Italy on October 11, 2010.

Study Design

This randomized, double-blind placebo-controlled Phase 3 study was conducted in 147 centres in 13 countries. Patients with metastatic advanced prostate cancer previously treated with docetaxel (N=1,195) were randomly assigned 2:1 to receive abiraterone acetate (1000 mg once daily) plus prednisone/prednisolone (5 mg twice daily) (N=797), or placebo plus prednisone/prednisolone (N=398). The primary endpoint was overall survival.

About Abiraterone Acetate

Abiraterone acetate is an investigational, oral medication being developed for the treatment of men with metastatic castration resistant prostate cancer who have received prior chemotherapy containing docetaxel.

Abiraterone acetate received approval from the U.S. Food and Drug Administration (FDA) on 28 April 2011. An application is pending with the European Medicines Agency.

About Metastatic Advanced Prostate Cancer

Metastatic castration-resistant prostate cancer or CRPC occurs when cancer has metastasized beyond the prostate and disease progresses despite serum testosterone below castrate levels.[6]

The prostate is a gland located around the urethra (under the bladder) in men that produces part of the seminal fluid.[7] In some cases, cancer of the prostate can grow slowly compared with other cancers. However, depending on factors including characteristics specific to the patient and the tumour, prostate cancer also can grow very quickly and spread widely.[8]

Globally, prostate cancer is the second most frequently diagnosed cancer in men and the fifth most common cancer overall.[9] Nearly 900,000 new cases of prostate cancer were diagnosed in 2008, including 36,700 inthe UK.[10] Additionally, in 2008, more than 258,000 men died from the disease, a 16 percent increase from 2002.[11],[12]

About Janssen

The Janssen Pharmaceutical Companies are dedicated to addressing and solving the most important unmet medical needs of our time. Our people, across many different companies, are united in their passionate pursuit of science for the benefit of patients. With employees in over 50 countries, we share the commitment of our corporate parents, to bring innovative ideas, products and services to patients throughout the world.

More information can be found at http://www.janssen.co.uk

About the Ortho Biotech Oncology Research & Development, Unit of Cougar Biotechnology, Inc.

Ortho Biotech Oncology Research & Development, Unit of Cougar Biotechnology, Inc. partners with affiliated units and companies in the Janssen Pharmaceutical Companies in the research and development of oncology and supportive care treatments.

[1] National Cancer Institute. Dictionary of Cancer Terms - Androgen. Available at: http://www.cancer.gov/dictionary?CdrID=45592.

[2] American Cancer Society. Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010.

[3] ZYTIGA (abiraterone acetate) Draft Label. November 2010.

[4] ZYTIGA (abiraterone acetate) Draft Label. November 2010.

[5] de Bono JS, Logothetis CJ, et al. Survival In Metastatic Prostate Cancer Treated with Abiraterone Acetate. New England Journal of Medicine. DRAFT MANUSCRIPT

[6] Hotte SJ, Saad F. Current management of castrate-resistant prostate cancer. Curr Oncol. 2010 September; 17(Supplement 2): S72-S79.

[7] An Introduction to Prostate Cancer. Prostate Cancer Foundation. 2009. Available at: http://www.prostatecancerfoundation.org/atf/cf/{705B3273-F2EF-4EF6-A653-E15C5D8BB6B1}/IntroProstateCancer.pdf. Accessed November 2009.

[8] Mayo Clinic. "Prostate Cancer." http://www.mayoclinic.com/health/prostate-cancer/DS00043. Accessed September 10, 2010.

[9] GLOBOCAN 2008 (IARC). "Prostate Cancer." http://globocan.iarc.fr/factsheets/cancers/prostate.asp. Accessed August 1, 2010.

[10] GLOBOCAN 2008 (IARC). "Prostate Cancer." http://globocan.iarc.fr/factsheets/cancers/prostate.asp. Accessed August 1, 2010.

[11] GLOBOCAN 2008 (IARC). "Prostate Cancer." http://globocan.iarc.fr/factsheets/cancers/prostate.asp. Accessed August 1, 2010.

[12] Parkin, D. et al. "Global Cancer Statistics 2002." CA Cancer J Clin (2005) 55;74-108.

SOURCE Janssen Pharmaceutical