US FDA grants full approval to DOXIL(R) for ovarian cancer progression following submission of phase III data

(I-Newswire) February 9, 2005 - The U.S. Food and Drug Administration (FDA) has granted full approval to DOXIL� (doxorubicin HCl liposome injection) for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy. DOXIL, marketed in the United States by Tibotec Therapeutics, Division of Ortho Biotech Products, L.P., originally received accelerated approval for refractory ovarian cancer in June 1999. As a result of the full approval, the product label for DOXIL has been updated to include survival, time to disease progression and tumor response rate data from a randomized Phase III clinical study.

Under accelerated approval, DOXIL was indicated for the treatment of metastatic ovarian cancer in patients with disease that was refractory to both paclitaxel- and platinum-based chemotherapy regimens. This approval was based on tumor response rates from three Phase II studies. According to the terms of the accelerated approval, Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) completed a randomized Phase III clinical study to formally demonstrate the drug's clinical benefit in patients with relapsed ovarian cancer. In March 2004, J&JPRD submitted a supplemental new drug application (sNDA) based on data from the Phase III study.

"The Phase III data provide evidence of the product's clinical benefit for patients with relapsed ovarian cancer," commented Alan N. Gordon, M.D., of the University of Arizona School of Medicine and Arizona Gynecologic Oncology, in Phoenix, Ariz., and lead author of the Phase III study, known as DOXIL Study 30-49.

In the randomized, multi-center, open-label, Phase III study, 474 patients with recurrent epithelial ovarian cancer were randomly assigned to receive either DOXIL 50 mg/m2 every 28 days or topotecan HCl 1.5 mg/m2/day for five consecutive days every 21 days. A total of 239 patients received DOXIL; 235 patients received topotecan HCl. The primary endpoint, time to disease progression after starting therapy, was comparable for the two treatment groups. The median time to disease progression was 4.1 months for the DOXIL group and 4.2 months for the topotecan HCl group; the p value, a statistical measurement, was 0.617. The overall median survival was 14.4 months for patients treated with DOXIL and 13.7 months for patients treated with topotecan HCl; the p value was 0.05. The p value was not adjusted for multiple comparisons. The overall tumor response rate for DOXIL-treated patients was 19.7 percent and 17 percent for topotecan-treated patients. The Phase III data were published in the September 2001 issue of the Journal of Clinical Oncology and in the October 2004 issue of the journal Gynecologic Oncology.

DOXIL is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

Myocardial damage may lead to congestive heart failure and may be encountered as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2. The use of DOXIL may lead to cardiotoxicity. DOXIL should be administered to patients with a history of cardiovascular disease only when the benefit outweighs the risk. Acute infusion-associated reactions have occurred in up to 10 percent of patients treated with DOXIL. Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have been reported. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. Severe myelosuppression may occur. Dosage should be reduced in patients with impaired hepatic function. Accidental substitution of DOXIL for doxorubicin HCl has resulted in severe side effects. DO NOT SUBSTITUTE. The use of DOXIL should be limited to physicians experienced in the use of cancer chemotherapeutic agents.

In clinical studies in recurrent ovarian cancer, the most common side effects reported with DOXIL therapy included hand-foot syndrome, nausea, mouth sores (stomatitis), tiredness, abdominal pain, vomiting, constipation, rash, fever, reduced red blood cell count (anemia), reduced white blood cell count (neutropenia), weakness, hair loss, appetite loss and diarrhea. Some patients experienced infusion-related reactions and skin reactions. Hand-foot syndrome, also known as palmar-plantar erythrodysesthesia (PPE), is characterized by symptoms of swelling, pain, redness and, for some patients, peeling of the skin on the hands and feet; in 23 percent of patients, these symptoms were severe. In some patients enrolled in DOXIL clinical trials, heart-related side effects were reported, some of which were severe. Due to the serious, potentially permanent effects of some of these events, including the potential for bone marrow suppression, close monitoring is necessary.

About Ovarian Cancer

Ovarian cancer is the most deadly form of gynecologic cancer. According to the American Cancer Society, an estimated 22,220 American women are expected to be diagnosed with ovarian cancer in 2005 and more than 16,000 of these women are expected to die from the disease. The Ovarian Cancer National Alliance reports that approximately 50 percent of women diagnosed with ovarian cancer die from it within five years. However, nearly 75 percent of ovarian cancer cases are diagnosed in later stages when the disease is more difficult to treat and the chance of five-year survival is only about 25 percent.

DOXIL Marketing and Development Information

DOXIL is marketed in the United States by Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., and in Israel by Janssen-Cilag. Schering-Plough Corporation, under a licensing agreement, has exclusive rights to market this medication as CAELYX� throughout the rest of the world, excluding Japan. J&JPRD and ALZA Corporation collaborated on the clinical development of DOXIL for ovarian cancer.

ALZA, J&JPRD and Tibotec Therapeutics all are part of the Johnson & Johnson Family of Companies, the world's most comprehensive and broadly based manufacturer of health care products.

ALZA, headquartered in Mountain View, Calif., is a leading developer of drug delivery-based pharmaceutical products, with the world's broadest array of technology platforms, including oral, transdermal, implantable, and liposomal technologies. More than 30 products marketed in over 80 countries worldwide now incorporate ALZA's drug delivery technologies.

J&JPRD, headquartered in Raritan, N.J., has nine sites throughout Europe and the United States. J&JPRD leverages drug discovery and drug development in a variety of therapeutic areas, including hematology, oncology, infectious disease, neurology and psychiatry, pain and women's health.

Tibotec Therapeutics, headquartered in Bridgewater, N.J., is dedicated to delivering innovative oncology, virology and other specialty therapeutics that improve patients' survival and quality of life, and address serious unmet needs in the health care community.

For more information about DOXIL and to see the full U.S. prescribing information, please visit www.DOXIL.com. For more information about the companies, visit the Tibotec Therapeutics Web site at http://www.tibotectherapeutics.com, the Johnson & Johnson Pharmaceutical Research & Development Web site at http://www.jnjpharmarnd.com or the ALZA Web site at http://www.alza.com.

Theresa Tamboer - Ttamboe2@gpcus.jnj.com
Johnson & Johnson Pharmaceutical Services, Inc

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