CORRECTING and REPLACING Follow-up Data Show ZYTIGA® Plus Prednisone Continues to Delay Progression of Metastatic Castration

  CORRECTING and REPLACING Follow-up Data Show ZYTIGA® Plus Prednisone
  Continues to Delay Progression of Metastatic Castration-Resistant Prostate
  Cancer in Patients without Prior Chemotherapy


Business Wire

BEERSE, Belgium -- February 13, 2013

Please replace the release with the following corrected version due to
multiple revisions.

The corrected release reads:


Note: Data in this release correspond to ASCO GU Abstract #5.

Janssen Research & Development, LLC [Janssen] announced today updated results
showing ZYTIGA^® (abiraterone acetate) plus prednisone continued to provide
statistically significant improvements in disease progression compared to
placebo plus prednisone, and longer overall survival in men with metastatic
castration-resistant prostate cancer.^1

The Phase 3, randomized, multicenter, placebo-controlled study (COU-AA-302)
also demonstrated statistically significant improvement compared to placebo in
the secondary endpoints of median time to opiate use for prostate cancer pain
and to initiation of chemotherapy. The data, from the latest pre-specified
interim analysis of the study, were presented today at the annual American
Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).

“These results show that the benefits of earlier use of abiraterone acetate
are sustained for many patients with metastatic castration-resistant prostate
cancer,” said Dana Rathkopf, MD, lead investigator of the study and assistant
attending physician in the Genitourinary Oncology Service at Memorial
Sloan-Kettering Cancer Center in New York City. “We were particularly pleased
with the long median overall survival among patients treated with abiraterone
acetate plus prednisone.”

Results from this most recent analysis and earlier interim analyses from
COU-AA-302 were the basis of the December 2012 U.S. Food and Drug
Administration (FDA) approval of an expanded indication for ZYTIGA^®, in
combination with prednisone, for the treatment of patients with mCRPC. The
European Commission has also approved an expanded indication for ZYTIGA^® for
the treatment of patients with mCRPC.

“It’s important that clinicians have proven treatments to offer patients with
metastatic castration-resistant prostate cancer before chemotherapy,” said
Michael L. Meyers, M.D., Ph.D., vice president, compound development team
leader, ZYTIGA^®, Janssen. “When ZYTIGA^® was first approved, it provided a
significant option for men with metastatic castration resistant disease after
chemotherapy with docetaxel; now, with its broader indication and supported by
the data presented at ASCO GU, we are pleased that more mCRPC patients may
benefit from this treatment option. The findings also broaden our knowledge
about the therapeutic activity of ZYTIGA^®.”

The analysis showed a statistically significant 47% reduction in risk of
disease progression – measured as radiographic progression-free survival
(rPFS) – in the ZYTIGA^® plus prednisone arm (ZYTIGA^® arm) compared to the
placebo plus prednisone arm (control arm). The median rPFS was 16.5 months in
the ZYTIGA^® arm vs. 8.3 months in the control arm [hazard ratio (HR) 0.53;
95% confidence interval (CI): 0.45 to 0.62; P<0.0001].

Treatment with ZYTIGA^® plus prednisone also resulted in an estimated 21%
reduction in risk of death [HR=0.79; 95% CI: 0.66, 0.96, P=0.0151]. The median
overall survival (OS) in the ZYTIGA^® arm was 35.3 months and was 30.1 months
in the control arm. At the time of this interim analysis, conducted when
approximately 55% of overall survival events (deaths) occurred, the
pre-specified p-value for statistical significance was not met.

Secondary Endpoints

Treatment with ZYTIGA^® plus prednisone also resulted in significant
improvements in all secondary study endpoints compared to the control arm,

  *39% decrease in the risk of initiation of cytotoxic chemotherapy for
    prostate cancer: a median of 26.5 months for the ZYTIGA^® arm vs. 16.8
    months for the control arm [HR=0.61 (95% CI: 0.51, 0.72); P<0.0001].
  *29% decrease in the risk of opiate use for cancer pain: the median time
    for the ZYTIGA^® arm was not reached and was 23.7 months for the control
    arm [HR=0.71; 95% CI: (0.59, 0.85); P<0.0002].

Safety Findings

No new safety concerns were identified with the longer treatment with ZYTIGA^®
compared to previously reported findings with the drug in mCRPC patients who
had prior chemotherapy. In this interim analysis, fatigue, fluid retention,
low blood potassium, hypertension, cardiac disorders and elevated liver
transaminase enzymes were adverse events (AEs) reported more frequently in the
ZYTIGA^® arm compared to the control arm. Patients in the ZYTIGA^® arm of the
study experienced more grade 3 and grade 4 AEs than those in the control arm.
Grade 3 or 4 AEs classified as liver toxicity, consisting primarily of
reversible elevations in liver transaminase enzymes, were reported in more
patients in the ZYTIGA^® arm than in the control arm.

Janssen previously announced that an Independent Data Monitoring Committee
(IDMC) unanimously recommended unblinding this Phase 3 study after an earlier
interim analysis 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 a Phase 3, randomized, double-blind, multicenter,
placebo-controlled international clinical study, which evaluated ZYTIGA^® plus
prednisone compared to placebo plus prednisone in 1,088 men with mCRPC who had
failed androgen deprivation therapy and had not received cytotoxic

Patients were randomized either to receive ZYTIGA^® 1 gram administered orally
once daily plus prednisone 5 milligrams (mg) administered orally twice daily,
or placebo orally daily plus prednisone 5 mg administered twice daily. The
co-primary endpoints of the study are rPFS and OS.

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Metastatic castration-resistant prostate cancer occurs when cancer has
metastasized (spread) beyond the prostate to other parts of the body and the
disease progresses despite serum testosterone below castrate levels.^2

The prostate is a gland in men that produces part of the seminal fluid and is
located around the urethra (under the bladder). In some cases, cancer of the
prostate can grow slowly. However, depending on factors including
characteristics specific to the patient and the tumour, prostate cancer also
can grow very quickly and spread widely.^3

In 2008, an estimated 370,000 new cases of prostate cancer were diagnosed in
Europe, and nearly 90,000 men died from the disease.^4

About ZYTIGA^®5

Since 2011, ZYTIGA^® has been approved in more than 65 countries worldwide,
many thousands of men have received treatment with it and it is quickly
becoming one of the cornerstones of Janssen’s oncology offerings.

ZYTIGA^® is the only approved therapy that inhibits production of androgen,
which fuels prostate cancer growth, via inhibiting the CYP17 enzyme complex
present at three sources: the testes, adrenals and the tumour itself.


In 2011, ZYTIGA^® in combination with prednisone/prednisolone was approved by
the European Commission (EC) for the treatment of metastatic
castration-resistant prostate cancer (mCRPC) in adult men whose disease has
progressed on or after a docetaxel-based chemotherapy regimen.

In December 2012, the EC granted an extension of the indication for ZYTIGA^®
(abiraterone acetate) permitting its use, in combination with prednisone or
prednisolone, for the treatment of metastatic castration-resistant prostate
cancer (mCRPC), in adult men who are asymptomatic or mildly symptomatic after
failure of androgen deprivation therapy in whom chemotherapy is not yet
clinically indicated.^5

Side Effects^5

                         Important Safety Information

  For a full list of side effects and for further information on dosage and
 administration, contraindications and other precautions when using ZYTIGA^®,
   please refer to ZYTIGA’s^® summary of product characteristics, which is
                 available at

Most common: urinary tract infection, hypokalaemia, hypertension, peripheral

Common: hypertriglyceridaemia, cardiac failure (including congestive heart
failure, left ventricular dysfunction and decreased ejection fraction), angina
pectoris, arrhythmia, atrial fibrillation, tachycardia, increased alanine
aminotransferase, fractures (includes all fractures with the exception of
pathological fracture), dyspepsia, haematuria and rash.

Uncommon: adrenal insufficiency.

About Janssen

The Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to
addressing and solving the most important unmet medical needs of our time,
including oncology, immunology, neuroscience, infectious disease, and
cardiovascular and metabolic diseases.

Driven by our commitment to patients, we develop innovative products, services
and healthcare solutions to help people throughout the world.

More information can be found at

                                    # # #


^1 Rathkopf D et al. Updated Interim Analysis (IA) of COU-AA-302, a Randomized
Phase 3 Study of Abiraterone Acetate (AA) in Metastatic Castration-resistant
Prostate Cancer (mCRPC) Patients (pts) Without Prior Chemotherapy. ASCO GU
2013; 14-17^th February: Abstract #5

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

^3 Mayo Clinic. “Prostate Cancer.” [last accessed
January 2013]

^4 [last accessed January 2013]

^5 ZYTIGA^® summary of product characteristics available on the EMA website:


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