EMBARGOED FOR RELEASE UNTIL MONDAY, MAY 16, 2011 AT 10:00 A.M.Contact: Wendy Waldsachs Isett, AUA410-977-4770, wisett@AUAnet.org ABIRATERONE DEMONSTRATES EFFECTIVE RESULTS WITH FAVORABLE SAFETY PROFILE IN MEN WITH CASTRATION-RESISTANT ADVANCED PROSTATE CANCERWASHINGTON, DC, May 16, 2011—Abiraterone acetate (AA) with low-dose prednisone (P) extended overallsurvival with favorable PSA and radiographic responses in patients with castration-resistant prostate cancerprogressing after docetaxel-based chemotherapy, according to updated data from COU-AA-301, a multi-institutional, randomized, double-blind, placebo-controlled, phase III study from researchers at 147institutions across 13 countries. AA is a selective androgen biosynthesis inhibitor that blocks the action of theCYP17 gene, which plays a vital role in androgen and estrogen biosynthesis.Data will be presented to the media during a special press conference on Monday, May 16, 2011 at 10:00 a.m.at the Walter E. Washington Convention Center in Washington, DC, during the 2011 Annual Meeting of theAmerican Urological Association (AUA). The session will be moderated by Christopher Amling, MD.The study included 1,195 patients with castration-resistant prostate cancer who had previously undergonechemotherapy with docetaxel. Patients were randomized 2:1 to receive 1,000 mg AA plus 5 mg P twice daily,or placebo. Patients were assessed using prostate-specific antigen (PSA) scores and radiographic tests.The study, of which the primary endpoint was overall survival, demonstrated: An increase in overall survival by a median of 14.8 months, compared to 10.9 with placebo. An improved time to PSA progression of 10.2 months That AA+P reduced the risk of death by 35 percent (HR=0.65) compared with placebo.AA+P demonstrated a favorable safety profile compared to placebo, with patients experiencing less fatigue (8percent vs. 10 percent), back pain (6 percent vs. 10 percent) and spinal cord compression (3 percent vs. 5percent). The most common grade 3/4 adverse events were decreased lymphocyte levels (21 percent vs. 23percent), fluid retention (2.3 percent vs. 1 percent), hypokalemia (3.9 percent vs. 0.8 percent), liver functiontest abnormalities (3.5 percent vs. 3.0 percent), hypertension (1.3 percent vs. 0.3 percent) and cardiacdisorders (4.1 percent vs. 2.3 percent).“In men with metastatic prostate cancer, hormone therapy typically slows disease progression for asubstantial time. Chemotherapy becomes an option when the disease no longer responds to standardhormone therapy,” Dr. Amling said. “But what happens when prostate cancer progresses after chemotherapy?
By targeting persistent androgen synthesis, these data suggest that abiraterone, combined with low-doseprednisone, may be an option.”NOTE TO REPORTERS: Experts are available to discuss this study outside normal briefing times. To arrangean interview with an expert, please contact the AUA Communications Office at the number above or e-mailwisett@AUAnet.org.About the American Urological Association: Founded in 1902 and headquartered near Baltimore, Maryland, theAmerican Urological Association is the pre-eminent professional organization for urologists, with more than 17,000members throughout the world. An educational nonprofit organization, the AUA pursues its mission of fostering thehighest standards of urologic care by carrying out a wide variety of programs for members and their patients. ###
705ABIRATERONE ACETATE PLUS LOW-DOSE PREDNISONE HAS A FAVORABLE SAFETY PROFILE, IMPROVESSURVIVAL AND PRODUCES PSA AND RADIOGRAPHIC RESPONSES IN METASTATIC CASTRATION-RESISTANTPROSTATE CANCER PROGRESSING AFTER DOCETAXEL-BASED CHEMOTHERAPY: RESULTS FROM COU-AA-301,A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE III STUDYFred Saad, Johann S. de Bono, Christopher M. Haqq, Christopher J. Logothetis, Karim Fizazi, Robert J. Jones,Kim N. Chi, Thian Kheoh, Howard I. Scher, Arturo Molina, Montreal, Canada INTRODUCTION AND OBJECTIVES: Abiraterone acetate (AA) is a selective androgen biosynthesis inhibitorthat blocks the action of CYP17 and potently inhibits persistent androgen synthesis (PAS) from adrenal andintratumoral sources. Early studies suggested that some castration-resistant prostate cancers (CRPCs) remaindependent on androgen receptor (AR) signaling. We recently reported that AA + prednisone (P) improvesoverall survival in mCRPC progressing after docetaxel (De Bono et al, ESMO 2010). Herein we provide updatedsafety outcomes and radiographic and PSA response data from this study.METHODS: In COU-AA-301 (NCT00638690), pts with docetaxel-treated mCRPC were randomized 2:1 to AA(1000 mg) + P (5 mg BID) (n=797) or placebo + P (n=398) at 147 centers in 13 countries. Safety assessmentswere standard; the primary endpoint was overall survival (OS). PSA and radiographic assessments wereadapted from the PCWG2 criteria (Scher, JCO, 2008).RESULTS: 1195 patients were enrolled. Based Efficacy Endpoints for Abiraterone Acetate vs. Placeboon a pre-specified interim analysis, the IDMCrecommended that the study be unblinded. Endpoint AA (n=797)Placebo (n=398) (95% P Value HR CI) Efficacyresults are presented in the table below. Grade OS, median3/4 adverse events (AEs) occurred in 55% of 14.8 mos 10.9 mos 0.65 (0.54, 0.77) <0.0001 pts withAA vs 58% with placebo. Frequently TTPP, median 10.2 mos 6.6 mos 0.58 (0.46, 0.73) <0.0001occurring (> 5%) AEs with AA vs placebo were:fatigue (8% vs 10%), anemia (7.5% vsrPFS, median 7.4%), 5.6 mos 3.6 mos 0.67 (0.58, 0.78) <0.0001 backpain (6% vs 10%), and spinal cord PSA responsecompression (3% vs 5%); the most common 38% 10% - <0.0001 grade3/4 AEs were decreased lymphocytes (21% responsea 14% (n=55/392) (n=5/181) b (2.1, 12.5) Objective 2.8% 5.1 <0.0001 vs 23%)and increased ALP (18% vs 13%). Grade 3/4 AEs of aspecial interest (AA vs placebo) were:RECIST in subjects with measurable disease at baseline; brelative risk. fluidretention (2.3% vs 1%), hypokalemia (3.8% vs0.8%), LFT abnormalities (3.5% vs 3.0%), hypertension (1.3% vs 0.3%), and cardiac disorders (4.1% vs 2.3%).CONCLUSIONS: AA + P significantly improves OS, TTPP, rPFS, PSA response rate, and radiologic response rateby RECIST criteria with a favorable safety profile in pts with mCRPC post docetaxel. This trial confirms that AAprovides clinical benefit by targeting PAS and AR signaling following medical/surgical castration and docetaxelin pts with mCRPC.