Janssen Submits Additional Marketing Applications for ZYTIGA® in the U.S. and European Union

RARITAN, N.J., June 15, 2012 /PRNewswire/ -- Janssen Research & Development, LLC announced today it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for ZYTIGA® (abiraterone acetate); simultaneously, Janssen-Cilag International NV has submitted a type II variation to the European Medicines Agency (EMA).  Both applications are intended to extend the use of ZYTIGA administered with prednisone to include the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy and before chemotherapy.  

ZYTIGA in combination with prednisone was approved in the U.S. in April 2011 and in the European Union in September 2011 for the treatment of men with mCRPC who have received prior docetaxel-based chemotherapy.  Since its first approval in the U.S. in 2011, ZYTIGA has been approved in more than 45 countries. The sNDA filing was completed by Janssen Research & Development on behalf of Janssen Biotech, Inc., the U.S. marketer of ZYTIGA.

Both regulatory applications follow the announcement of results observed from pre-specified interim analyses of the international Phase 3, randomized, double-blind, placebo-controlled COU-AA-302 clinical study.  This study, which included 1,088 asymptomatic or mildly symptomatic men with mCRPC who had not received chemotherapy, evaluated the efficacy and safety of ZYTIGA plus prednisone compared to placebo plus prednisone, using co-primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS).  Data from this study were presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) earlier this month.

"We're delighted to move forward so quickly with these regulatory submissions, building on the momentum created by the data presentation two weeks ago," said Michael L. Meyers, M.D., Ph.D., Vice President, Compound Development Team Leader, ZYTIGA.  "We look forward to working with the FDA and EMA to make ZYTIGA available for men with metastatic prostate cancer earlier in the course of their disease."

The company previously announced the study was unblinded based on the unanimous recommendation of an Independent Data Monitoring Committee (IDMC).  Based on these results, the IDMC also recommended that patients in the control arm be offered treatment with ZYTIGA.

"As a company, we strive to develop innovative therapeutic options that meet the unmet needs of patients suffering from devastating diseases such as mCRPC," said William N. Hait, M.D., Ph.D., Global Head, Janssen Research & Development and Head, Oncology Therapeutic Area.  "These regulatory submissions for ZYTIGA are a clear example of our efforts to bring extraordinary oncologic therapies to those with the greatest need."

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) who have received prior chemotherapy containing docetaxel.

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-infinity (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 (greater than or equal to 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.

SOURCE Janssen Research & Development, LLC

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