Chiron and Ciba announce FDA market clearance of Aredia(R) for treatment of patients with Osteolytic Bone Metastases of breast cancer; First Therapeutic For Osteolytic Bone Metastases Associated with Breast Cancer.

EMERYVILLE, Calif. and SUMMIT, N.J.--(HealthWire)--August 12, 1996-- Chiron Therapeutics, a business unit of Chiron Corporation (Nasdaq: CHIR), and Ciba Pharmaceuticals, a division of Ciba-Geigy Corporation jointly announced today that the United States Food and Drug Administration (FDA) has cleared Aredia(R) (pamidronate disodium for injection) for marketing for the treatment of patients with osteolytic bone metastases of breast cancer, in conjunction with standard antineoplastic therapy. Aredia is the first drug that has been proven to reduce the incidence of skeletal complications of metastatic breast cancer, thereby reducing the need for radiation therapy or surgery to the bone. It has also been shown to provide relief of bone pain caused by metastatic breast cancer, thereby reducing the need for narcotic analgesics. The drug is also indicated for the treatment of osteolytic bone lesions of multiple myeloma, moderate-to-severe hypercalcemia of malignancy and moderate-to-severe Paget's disease.

Breast cancer is diagnosed in approximately 184,000 women each year, and has the highest incidence of associated metastatic bone disease among all cancers. Approximately 100,000 breast cancer patients are currently living with cancer that has metastasized to the bone. Patients with osteolytic bone metastases often suffer from skeletal complications, including pathologic bone fractures, spinal cord compression, impaired mobility, and chronic and debilitating bone pain.

"Women with advanced breast cancer are increasingly educated medical consumers who are actively involved in managing their disease," said Amy Langer, Executive Director of the National Alliance of Breast Cancer Organizations (NABCO), a leading non-profit information resource and network of 375 breast cancer organizations. "Aredia will be an important treatment option, and treatment options are what breast cancer patients need and deserve."

The marketing clearance was based upon data from two large, placebo-controlled, double-blind, multicenter studies in breast cancer patients with osteolytic bone metastases. These studies enrolled 372 patients treated with hormonal therapy and 382 patients treated with chemotherapy. All patients enrolled had stage IV breast cancer with two or more predominantly lytic lesions, with at least one lesion that was one centimeter or greater in diameter. Patients were randomized to receive Aredia 90mg every three to four weeks via two-hour IV infusions for 12 months or matching placebo, in conjunction with either hormonal therapy or chemotherapy. The studies demonstrated that patients receiving Aredia had a significant reduction in skeletal complications, the primary endpoint, and significant relief of bone pain, a secondary endpoint. The Aredia treatment effect appeared to be less pronounced in the study of breast cancer patients receiving hormonal therapy than in the study of those receiving chemotherapy. Additionally, patients receiving Aredia had fewer pathologic fractures and a decreased need for radiation therapy for pain or skeletal complications.

"These data demonstrate that Aredia effectively reduces skeletal complications, bone morbidity and the debilitating bone pain associated with bone metastases in advanced breast cancer patients over a 12-month period," said Gabriel Hortobagyi, M.D., Professor of Medicine and Chairman of the Department of Breast/Gyn at M.D. Anderson Cancer Center. "Aredia can help improve the clinical management of advanced breast cancer patients and may enhance the quality-of-life of these patients."

In these studies, skeletal morbidity was defined as the mean number of skeletal complications (pathologic fractures, spinal cord compression, radiation therapy or surgery to bone) per patient per year. In patients receiving concomitant chemotherapy, Aredia provided a 36% reduction in the skeletal morbidity rate (2.1 vs. 3.3 with placebo, P<0.01). In patients receiving concomitant hormonal therapy, skeletal morbidity was reduced by 31% with Aredia (2.4 vs. 3.5, P=0.05). For an average patient, these reductions mean one fewer major skeletal complication per year with Aredia.

Additional results of the trials show that patients treated with Aredia had fewer skeletal complications than those patients who received placebo. Also, fewer Aredia-treated patients required radiation therapy for pain, or to prevent or treat fractures, compared to patients treated with placebo. Among patients who had pain at the beginning of the trials, Aredia-treated patients had less severe pain, and experienced pain less often, in comparison to patients who did not receive Aredia. Additionally, Aredia-treated patients also had a decreased need for strong pain medication, unlike patients receiving placebo. The statistical significance of these results may be overstated due to numerous analyses.

The incidence and type of adverse events with Aredia were similar to those with placebo, with most events likely due to the underlying disease or concomitant antineoplastic therapy. The most frequent adverse events were fatigue, fever, nausea, vomiting, anemia, and skeletal pain. Transient arthralgias and myalgias were reported slightly more frequently with Aredia than with antineoplastic therapy alone (12% and 23% vs. 8% and 17%, respectively). Serum calcium and electrolytes must be closely monitored, as must patients with preexisting anemia, leukopenia or thrombocytopenia.

"This new indication for Aredia will provide much needed relief and reduction of skeletal risk for the thousands of women who suffer from the pain and bone complications of breast cancer. Importantly, the two large clinical trials we performed demonstrated that Aredia is well-tolerated in these patients," said John J. Seaman, Pharm.D., Director of Clinical Development at Ciba Pharmaceuticals.

"Aredia is becoming a valuable component of our growing portfolio of oncology products. The data from the clinical trials demonstrate the drug's considerable efficacy for reducing the incidence, morbidity and pain of skeletal complications arising from metastatic breast cancer," said Edward Kenney, Division Vice President at Chiron Therapeutics. "The addition of this new indication, as well as its other uses, demonstrates the clinical benefits of Aredia in treating metastatic and metabolic bone diseases."

Aredia was cleared for marketing in the U.S. by the FDA in September 1995 for the treatment of osteolytic bone lesions in patients with multiple myeloma in conjunction with standard anti-myeloma chemotherapy. It was the first drug to be approved for this indication and has been on the market since 1991 for the treatment of cancer-related bone disorders. Chiron Therapeutics exclusively markets Aredia for the United States under a marketing agreement with Ciba Pharmaceuticals.

Chiron Corporation is a science-driven health company that combines diagnostic, vaccine and therapeutic strategies for controlling disease. Headquartered in Emeryville, California, with operations on four continents, Chiron had revenues in 1995 of $1.1 billion. Chiron participates in four global healthcare markets: diagnostics, including immunodiagnostics, critical care diagnostics and new quantitative probe tests; therapeutics, with an emphasis on oncology and infectious disease; pediatric and adult vaccines; and ophthalmic surgical products for the correction of vision. Chiron also has research programs in gene therapy, combinatorial chemistry, cancer, infectious and cardiovascular disease, and critical care.

Ciba Pharmaceuticals is a division of Ciba-Geigy Corporation of Tarrytown, NY, a wholly-owned subsidiary of Ciba-Geigy Limited of Basel, Switzerland. Ciba is a leading developer and manufacturer of healthcare and agricultural products and speciality chemicals for industry. Ciba Pharmaceuticals is dedicated to discovering, developing, manufacturing and marketing innovative pharmaceuticals that meet unmet medical needs and improve patients' quality of life. Ciba Pharmaceuticals has a major worldwide commitment to the research and development of new therapeutic modalities for the treatment of cancer.

For more information about Aredia for breast cancer or multiple myeloma patients, please call Chiron's Professional Services group at 1-800-CHIRON-8 (1-800-244-7668), selection #2.

CONTACT: Chiron Corporation

Larry Kurtz, Vice President, Corporate Communications

510/601-2476

Kimberly Sankaran, Manager, Corporate Communications

510/601-2412

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Burns McClellan, Inc.

Karen L. Bergman,

James W. Heins

212/505-1919