Abiraterone Acetate Significantly Improved Overall Survival for Patients with
Metastatic Advanced Prostate Cancer

    
     Results observed in patients treated with abiraterone acetate plus
           prednisone/prednisolone whose disease progressed after
                         docetaxel-based chemotherapy

      Based on the results of this Phase 3 study, Janssen plans to file
       marketing applications for abiraterone acetate with regulatory
                            authorities worldwide
    

TORONTO, Oct. 12 /CNW/ - Results from a pre-specified interim analysis of a randomized, placebo-controlled Phase 3 study, COU-AA-301, demonstrate that patients treated with the investigational agent abiraterone acetate plus low dose prednisone/prednisolone showed a significant improvement in overall survival compared to patients treated with prednisone/prednisolone plus placebo. This study included 1,195 patients worldwide, including 154 Canadian patients, with metastatic advanced prostate cancer (also referred to as castration-resistant prostate cancer, or CRPC) previously treated with one or two chemotherapy regimens, at least one of which contained docetaxel.

The results of this randomized, placebo-controlled study were shared during a late-breaking presentation at the Presidential Symposium at the 35th Annual European Society for Medical Oncology (ESMO) Congress.

Treatment with abiraterone acetate resulted in a 35 per cent reduction in the risk of death (HR=0.65; 95 per cent CI: 0.54, 0.77; p(less than)0.0001) and a 36 per cent increase in median survival (14.8 months vs. 10.9 months) compared with placebo.

Patients who received abiraterone acetate and low dose 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=0.58 (95 per cent CI: 0.46, 0.73); p(less than)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=0.67 (95 per cent CI: 0.58, 0.78); p(less than)0.0001). Total PSA response, defined as greater than or equal to a 50 per cent decrease from baseline, was achieved in 38 per cent of patients treated with abiraterone acetate vs. 10 per cent in the prednisone/prednisolone plus placebo group (p(less than)0.0001).

Patients in the abiraterone acetate group experienced more mineralocorticoid-related adverse events than those in the prednisone/prednisolone plus placebo group. The most frequent adverse events were fluid retention (30.5 per cent vs. 22.3 per cent) and hypokalemia (17.1 per cent vs. 8.4 per cent). Grade 3/4 hypokalemia and hypertension were more frequent in the abiraterone acetate arm than in the placebo arm (3.8 per cent vs. 0.8 per cent and 1.3 per cent vs. 0.3 per cent, respectively). Liver function test abnormalities were observed in 10.4 per cent of abiraterone acetate treated patients compared to 8.1 per cent in the prednisone/prednisolone plus placebo group. Cardiac disorders were observed in 12.5 per cent of abiraterone acetate patients vs. 9.4 per cent of patients who received placebo. Mechanism-based adverse events were amenable to medical management and distinct from adverse events commonly associated with cytotoxic chemotherapy.

"Abiraterone has the potential to meet a significant unmet need so this news will be incredibly important to prostate cancer patients and their families," said Johann S. de Bono, MD, FRCP, MSc, PhD, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, one of the lead COU-AA-301 investigators. "We are very pleased with the definitive results of this rigorous study, which show that abiraterone acetate may extend survival for men with metastatic advanced prostate cancer that progressed after treatment with docetaxel."

Janssen-Ortho Inc. will have the marketing rights to abiraterone acetate in Canada. In Canada, abiraterone acetate has not received marketing authorization and is for investigational use only. Based on the positive results of the Phase 3 study, COU-AA-301, Janssen is planning for marketing applications with regulatory authorities worldwide.

"Prevalence rates for prostate cancer in Canada have been increasing over the past 30 years and the disease is one of the most common cancers among men in Canada," said Dr. Fred Saad, Chief of Urology and Director of Urologic Oncology, University of Montreal Hospital Center and COU-AA-301 trial investigator. "If detected early, prostate cancer can often be managed effectively, but for patients with late-stage metastatic, castration-resistant prostate cancer, there are few available treatment options. The results of this study are encouraging because they show there is a new treatment option for patients in the advanced stage of the disease."

A program that provides early access to abiraterone acetate for eligible patients is expected to be opened in the United States in October and will be opened in sites outside the United States in the following months, with the timing of the program contingent on local health authority and ethics committee approvals.

"The results of this abiraterone acetate Phase 3 study in patients with metastatic advanced prostate cancer bring us closer to achieving our goal of developing extraordinary preventive, diagnostic and therapeutic solutions based on our tumour microenvironment strategy," said William N. Hait, MD, PhD, Global Therapeutic Head, Oncology, Ortho Biotech Oncology Research & Development. "We believe that abiraterone acetate is an important medical advance, and we look forward to further developing oncology therapeutic options that may impact patients' lives."

Ortho Biotech Oncology Research & Development, a unit of Cougar Biotechnology, Inc., previously announced that the Independent Data Monitoring Committee recommended unblinding this Phase 3 study after a pre-specified interim analysis demonstrated a statistically significant improvement in median overall survival and an acceptable safety profile. The IDMC also recommended that patients in the prednisone/prednisolone plus placebo group be offered treatment with abiraterone acetate.

Study Design

This randomized, double-blind placebo-controlled Phase 3 study was conducted in 147 centers in 13 countries including 12 centers in Canada. 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 a novel, targeted, investigational, oral androgen biosynthesis inhibitor being developed for the treatment of metastatic advanced prostate cancer that has progressed after developing resistance to conventional hormonal therapies. This is also known as castration-resistant prostate cancer (CRPC).

About Prostate Cancer

Prostate cancer occurs when cancer cells form in the tissues of the prostate. The prostate is a gland located around the urethra (under the bladder) in men that produces part of the seminal fluid(1). 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 can also grow very quickly(2) and spread to other places such as the lymph nodes, bones or other parts of the body. Prostate cancer is considered to be advanced once it has spread beyond the prostate region(1).

Prostate cancer is the most common cancer among men in Canada (excluding non-melanoma skin cancer). It is estimated that approximately 24,600 men will be diagnosed with prostate cancer in Canada in 2010, and one in seven Canadian men will develop prostate cancer during his lifetime(3). The incidence rate of prostate cancer has been increasing since 1980, likely due to an increased rate of early detection and the aging population since the chances of developing prostate cancer increases with age(3). But according to Prostate Cancer Canada, prostate cancer is turning up in men in their 40s(4).

While 90 per cent of prostate cancer cases are curable if detected and treated early(4), an estimated 4,300 Canadian men will die of the disease in 2010(3). On average, 80 Canadian men will die of prostate cancer every week(3). Fortunately, death rates have been declining since the mid-1990s, which is likely due to early detection, better treatment or both(4).

Globally, prostate cancer is the second most frequently diagnosed cancer in men and the fifth most common cancer overall(5). More than 900,000 new cases of prostate cancer were diagnosed in 2008 and more than 258,000 men died from the disease, a 16 per cent increase from 2002(5)(6).

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

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

About Janssen

Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to addressing and solving the most important unmet medical needs of our time, including oncology (e.g. multiple myeloma and prostate cancer), immunology (e.g. psoriasis), neuroscience (e.g. schizophrenia, dementia and pain), infectious disease (e.g. HIV/AIDS, Hepatitis C and tuberculosis), and cardiovascular and metabolic diseases (e.g. diabetes).

Driven by our commitment to patients, we develop sustainable, integrated healthcare solutions by working side-by-side with healthcare stakeholders, based on partnerships of trust and transparency.

More information can be found at www.janssen-emea.com

About Janssen-Ortho Inc.

Janssen-Ortho Inc. is a healthcare company committed to providing Canadians with innovative treatment options that enhance and improve life. Headquartered in Toronto, the company offers a broad range of medications used in psychiatry, dementia, attention deficit hyperactivity disorder, psoriasis, pain management, women's health, infectious disease, anemia, oncology, and virology.

(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from J&JPRD and/or Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 3, 2010. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither J&JPRD nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

    
    References
    -------------------------
    (1) National Cancer Institute. "What You Need to Know About Prostate
    Cancer." http://www.cancer.gov/cancertopics/wyntk/prostate/page1
    September 10, 2010 at.

    (2) Mayo Clinic. "Prostate Cancer."
    http://www.mayoclinic.com/health/prostate-cancer/DS00043. September 10,
    2010 at.

    (3) Prostate Cancer Statistics. Canadian Cancer Society. Available at: 
http://www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Stats%20at%20a%20glance/Prostate%20cancer.aspx?sc_lang=en.
    Accessed August 2010.

    (4) Statistics. Prostate Cancer Canada. Available at: 
http://www.prostatecancer.ca/Prostate-Cancer/Prostate-Cancer/Statistics.aspx.
    Accessed August 2010.

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

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

For further information: Collin Matanowitsch, MS&L, 416-847-1330, [email protected]; Suzanne Frost, Janssen-Ortho Inc., 416-449-9444, [email protected]