Raritan, NJ, December 12, 2012 – Janssen Research & Development, LLC announced today that results from analyses of COU-AA-302, a Phase 3, randomized, placebo-controlled study of ZYTIGA® (abiraterone acetate) plus prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) prior to chemotherapy, have been published online in The New England Journal of Medicine.
This study was the basis of Monday’s U.S. Food and Drug Administration (FDA) approval of an expanded indication of ZYTIGA, in combination with prednisone, in metastatic castration-resistant prostate cancer. Previously, ZYTIGA with prednisone had only been approved for use in men with mCRPC after chemotherapy.
“These results, now published in a major peer-reviewed medical journal, highlight the value of earlier use of ZYTIGA in treating metastatic castration-resistant prostate cancer and advance our understanding of the role of its mechanism of action,” said Charles J. Ryan, M.D., lead investigator of the study and associate professor of clinical medicine at the UCSF Helen Diller Family Comprehensive Cancer Center.
“This certainly has been an exciting week for Janssen,” said Michael L. Meyers, M.D., Ph.D., vice president, compound development team leader, ZYTIGA. “But more importantly, these milestones mean men living with this devastating disease have a new treatment option before chemotherapy.”
Since its first approval in the U.S. in 2011, ZYTIGA has been approved in more than 65 countries. More than 40,000 men worldwide have received treatment with it, and it is quickly becoming one of the cornerstones of treatment for mCRPC.
About the COU-AA-302 Study
Data from 1,088 asymptomatic or mildly symptomatic patients with mCRPC who had not received chemotherapy showed that ZYTIGA plus prednisone (ZYTIGA arm) produced statistically significant improvements in radiographic progression-free survival and other prospectively defined efficacy endpoints compared to placebo plus prednisone (control arm), including time to initiation of cytotoxic chemotherapy and time to initiation of opioid use for cancer pain. The results also showed longer overall survival, the co-primary endpoint, in the ZYTIGA arm compared to the control arm.
Fatigue, arthralgia (joint pain) and peripheral edema (foot, leg, and ankle swelling) were among the 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, more serious AEs and more AEs with an outcome of death. Grade 3 or 4 AEs classified as liver toxicity, consisting primarily of reversible elevations in liver transaminase enzymes, were reported in both arms. No patient in either treatment group died from liver toxicity-related AEs.
More information about ZYTIGA can be found at www.zytiga.com.
Indication
ZYTIGA® (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).
IMPORTANT SAFETY INFORMATION
Contraindications - ZYTIGA® (abiraterone acetate) is not indicated for use in women. ZYTIGA® can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant.
Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess - Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in study 1) or NYHA Class II to IV heart failure (in study 2) because these patients were excluded from these randomized clinical trials. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.
Adrenocortical Insufficiency (AI) - AI was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.
Hepatotoxicity - Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function.
Increased ZYTIGA® Exposures with Food - ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.
Adverse Reactions - The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.
The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.
Drug Interactions - ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration with CYP2D6 substrates that have a narrow therapeutic index. If an alternative cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. In vitro, ZYTIGA® inhibits CYP2C8. There are no clinical data on its use with drugs that are substrates of CYP2C8. Patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.
Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. The effects of strong CYP3A4 inhibitors or inducers on the pharmacokinetics of abiraterone have not been evaluated, in vivo. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution during treatment with ZYTIGA®.
Use in Specific Populations - Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C).
For more information please see the accompanying full prescribing information or visit www.zytiga.com.
About Janssen Research & Development, LLC
Janssen Research & Development, LLC is headquartered in Raritan, N.J. and has affiliated facilities in Europe, the United States and Asia. Janssen Research & Development is leveraging a combination of internal and external innovation to discover and develop novel medicines and solutions in five distinct therapeutic areas: Neuroscience, Oncology, Immunology, Infectious Diseases and Vaccines, and Cardiovascular and Metabolism. For more information about Janssen Research & Development, LLC visit www.janssenrnd.com.
Janssen Research & Development is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Driven by our commitment to patients, we work together to bring innovative ideas, products, services and solutions to address serious unmet medical needs around the world.
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