RARITAN, NJ, August 29, 2012 – Janssen Research & Development, LLC, announced today that the U.S. Food and Drug Administration (FDA) has granted Priority Review to the supplemental New Drug Application (sNDA) for ZYTIGA® (abiraterone acetate) administered in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy.
The FDA grants Priority Review to medicines that may offer major advances in treatment, or provide a treatment option where no adequate therapy exists. Under the Prescription Drug User Fee Act (PDUFA), the FDA will aim to conclude its review within six months of the sNDA submission. The sNDA was submitted in June.
“We believe that men with mCRPC whose disease is asymptomatic or mildly symptomatic, for whom chemotherapy may not be immediately necessary, have limited treatment options and that this disease setting represents a critical unmet medical need,” said Michael L. Meyers, M.D., Ph.D., Vice President, Compound Development Team Leader, ZYTIGA. “We are delighted the FDA has granted a Priority Review designation for our sNDA.”
The ZYTIGA sNDA submission is based on the efficacy and safety results of an international Phase 3, randomized, double-blind, placebo-controlled clinical study that evaluated ZYTIGA plus prednisone compared to placebo plus prednisone in 1,088 asymptomatic or mildly symptomatic men with mCRPC who had not received chemotherapy. Data from this study were presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in June.
ZYTIGA in combination with prednisone was approved by the FDA in April 2011 for the treatment of patients with mCRPC who have received prior chemotherapy containing docetaxel.
More information about ZYTIGA can be found at www.zytiga.com.
Important Safety Information
Contraindications - ZYTIGA® (abiraterone acetate) may cause fetal harm (Pregnancy Category X) 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 hypertension, hypokalemia, and 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 because these patients were excluded from the randomized clinical trial. 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 has been reported in clinical trials 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 - Increases in liver enzymes have led to drug interruption, dose modification, and/or discontinuation. 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.
Food Effect - ZYTIGA® must be taken on an empty stomach. Exposure of abiraterone increases up to 10-fold when abiraterone acetate is taken with meals. 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 (≥5%) are joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, fractures and upper respiratory tract infection.
Drug Interactions - ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid coadministration 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. Additionally, abiraterone is a substrate of CYP3A4 in vitro. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution.
Use in Specific Populations - The safety of ZYTIGA® in patients with baseline severe hepatic impairment has not been studied. These patients should not receive ZYTIGA®.
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.
Kellie McLaughlin, Janssen Global Services, LLC
Lisa Vaga, Janssen Biotech, Inc.