Note: Data in this release correspond to ASCO GU Abstract #5.
Follow-up Data Show ZYTIGA® Plus Prednisone Continues to Delay Progression of Metastatic Castration-Resistant Prostate Cancer inPatients without Prior Chemotherapy Beerse, Belgium, 13 February, 2013 – 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. 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, specifically:
• 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 previouslythat 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 chemotherapy.
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. 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. In 2008, an estimated 370,000 new cases of prostate cancer were diagnosed in Europe, and nearly 90,000 men died from the disease. About ZYTIGA®
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. Indicati 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 Side Effect 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 oedema 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.
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References
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; 14-17th 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]
5 ZYTIGA® summary of product characteristics available on the EMA website:
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more mCRPC patients may benefit from this treatment option. The findings also broaden our knowledge 
Patients were randomized either to receive ZYTIGA® 1 gram administered orally once daily plus 
Most common: urinary tract infection, hypokalaemia, hypertension, peripheral oedema