Abiraterone Acetate Significantly Improves Overall Survival of Patients With Post-Chemotherapy Metastatic Castration-Resistant Prostate Cancer

By Janssen Pharmaceutical, PRNE
Tuesday, May 24, 2011

HIGH WYCOMBE, England, May 25, 2011 -

- 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

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

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 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: 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.

[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: www.prostatecancerfoundation.org/atf/cf/{705B3273-F2EF-4EF6-A653-E15C5D8BB6B1}/IntroProstateCancer.pdf.
Accessed November 2009.

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

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

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

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

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

Media contact: Donna Cullan, +44-(0)-7901-227-391

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