Horsham, Pa., April 28, 2011- Centocor Ortho Biotech Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved ZYTIGA™ (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.
Androgens are hormones that promote the development and maintenance of male sex characteristics. However, in prostate cancer, androgens can help fuel the tumor's growth. Androgen production primarily occurs in the testes and adrenal glands; in men with prostate cancer, the tumor tissue is an additional source of androgens. ZYTIGA is an oral androgen biosynthesis inhibitor that works by inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources.
"This FDA approval represents a welcome new option in the treatment of metastatic prostate cancer," said Howard Scher, MD, Chief of the Genitourinary Oncology Service, Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan-Kettering, and one of the co-lead investigators for the Phase 3 clinical study. "As a clinician, I believe the efficacy and safety profile of abiraterone acetate, as well as its oral, once-daily formulation, will help address the important need for additional therapeutic choices for men living with this serious disease."
"In a Phase 3 study, treatment with ZYTIGA plus prednisone showed a significant increase in median survival compared with placebo plus prednisone," said Professor Johann S. de Bono, MD, FRCP, MSc, PhD, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, and one of the co-lead investigators for the Phase 3 clinical study. "It's an exciting time for men with prostate cancer, and I believe that ZYTIGA will play an essential role in clinical practice."
Results of the pivotal Phase 3, randomized, placebo-controlled, multicenter study showed that at pre-specified interim analysis, treatment with ZYTIGA in combination with prednisone resulted in a 35 percent reduction in the risk of death (14.8 months vs. 10.9 months [hazard ratio (HR) = 0.646; 95 percent CI: 0.543, 0.768; p<0.0001]) and a 3.9 month difference in median survival compared to placebo plus prednisone. In an updated analysis, results were consistent with those from the interim analysis with a 4.6 month difference between the two arms in median survival (15.8 months vs. 11.2 months [HR = 0.74]).
At a predetermined number of events in the study, an interim analysis was conducted and it was determined that efficacy had been demonstrated. At that time, the study was unblinded at the recommendation of the Independent Data Monitoring Committee. Information regarding these results can be found at: http://www.centocororthobiotech.com/cobi/viewDocumentByTitleAlias.html?title=PR_101110.
The most common adverse reactions (greater than or equal to 5 percent) reported in the clinical study were: joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia and upper respiratory tract infection. Additional information is included in the Important Safety Information below.
"Prostate cancer is a significant public health threat in the United States," said Wendy L. Poage, MHA, President, Prostate Conditions Education Council, a national organization committed to men's health. "ZYTIGA is an important new option and a welcome addition to the armamentarium we have to fight this deadly disease."
Pivotal Study Design
ZYTIGA, in combination with prednisone, was evaluated in a Phase 3, randomized, placebo-controlled, multicenter clinical study in patients who had received prior chemotherapy containing a taxane (N = 1,195). Patients were randomized 2:1 to receive ZYTIGA 1 gram daily in combination with prednisone 5 milligrams (mg) twice daily or placebo in combination with prednisone 5 mg twice daily (control arm).
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
ZYTIGA™ may cause fetal harm (Pregnancy Category X) and is contraindicated in women who are or may become pregnant.
Warnings and Precautions
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. Safety has not been established in patients with LVEF < 50% or NYHA Class III or IV heart failure. 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) has been reported in clinical trials 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 or if the patient experiences unusual stress. 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).
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.
The most common adverse reactions (?5%) reported in clinical trials were joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia and upper respiratory tract infection.
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. Additionally, abiraterone is a substrate of CYP3A4 in vitro. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution.
About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer or CRPC occurs when cancer has metastasized beyond the prostate and disease progresses despite serum testosterone below castrate levels.
The prostate is a gland located around the urethra (under the bladder) in men that produces part of the seminal fluid. In some cases, cancer of the prostate can grow slowly compared with other cancers. However, depending on factors including characteristics specific to the patient and the tumor, prostate cancer also can grow very quickly and spread widely.
Excluding skin cancer, prostate cancer is the most frequently diagnosed cancer in men in the United States. In 2010, more than 217,000 new cases of prostate cancer were estimated and more than 32,000 men died from the disease.
About ZYTIGA (abiraterone acetate)
ZYTIGA (abiraterone acetate) was developed by Ortho Biotech Oncology Research & Development, a Unit of Cougar Biotechnology, Inc., and will be marketed by Centocor Ortho Biotech Inc. Marketing applications for ZYTIGA have been filed with other regulatory authorities throughout the world.
ZYTIGA is the first oral, once-daily medication indicated for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel. For more information about ZYTIGA, visit www.ZYTIGA.com.
About Centocor Ortho Biotech Inc.
Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology and oncology. Built upon a pioneering history, Centocor Ortho Biotech Inc. harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options. Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates and health care professionals have access to the latest treatment information, support services and quality care. In addition to metastatic castration-restistant prostate cancer, Centocor Ortho Biotech markets oncology treatments for diseases such as recurrent ovarian cancer, relapsed or refractory multiple myeloma, hairy cell leukemia and anemia due to the effect of concomitantly administered chemotherapy. For more information about Centocor Ortho Biotech, visit www.centocororthobiotech.com.
Centocor Ortho Biotech Inc. is a member of the Johnson & Johnson Family of Companies.
About the Ortho Biotech Oncology Research & Development, unit of Cougar Biotechnology, Inc.
Ortho Biotech Oncology Research & Development, Unit of Cougar Biotechnology, Inc., partners with affiliated units and companies in the Janssen Pharmaceutical Companies, such as Centocor Ortho Biotech Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C., in the research and development of oncology and supportive care treatments.
* NOTE: Centocor Ortho Biotech Inc. provides support to Prostate Conditions Education Council for initiatives benefitting prostate cancer patients.