Pamidronate Disodium Therapy for Improved Patient Outcome Presented at American Society of Hematology.

SEATTLE--(BUSINESS WIRE)--Dec. 4, 1995--Today at the American Society of Hematology's (ASH) 37th Annual Meeting & Exposition researchers from UCLA School of Medicine presented results from a 21-month, Phase III clinical study showing that "Long-term Pamidronate Disodium Therapy Leads to a Reduction in Skeletal Related Episodes in Stage III Multiple Myeloma Patients, and an Improvement in Survival in Those on Salvage Therapy."

Aredia (pamidronate disodium for injection) is the first medical therapy proven to reduce pathological fractures and other skeletal complications in patients with multiple myeloma.

This data was presented during the ASH scientific session "Multiple Myeloma and CLL II" at the Sheraton Grand Ballroom B in Seattle at 3 p.m. PST. The trial's principal investigator, James Berenson, M.D., Associate Professor of Medicine, UCLA School of Medicine, and Chief of Medical Oncology, DVA Medical Center, West Los Angeles, reviewed results of a large, multicenter, placebo-controlled study in which 392 patients were randomized to receive 21 months of treatment with 90mg/month of Aredia or placebo. Of 392 patients, there were 377 evaluable patients; 198 Aredia and 179 placebo.

In this study, patients were stratified by antimyeloma chemotherapy at trial entry (stratum 1-1st line therapy; stratum 2 - greater than or equal to 2nd line therapy). The treatment groups were comparable for age, sex, stratum, serum beta-2 microglobulin levels, and antimyeloma chemotherapy. After 21 cycles, the proportion of patients experiencing any skeletal event remained smaller in the Aredia group than the placebo group (P=.015). In addition, the mean skeletal morbidity rate (#SREs/year) was 2.2 vs. 1.3 for placebo vs. Aredia patients (P=.008). Survival of all patients was not different between treatment groups (Aredia vs. placebo) via log-rank analysis of the Kaplan-Meier estimates. However, stratum 2 patients (on salvage chemotherapy) receiving Aredia showed a significant improvement in survival (median 20.6 mos. vs. 14.1 mos. for placebo group, P=.041) when adjusting for the only prognostic factors found to be significant for survival in this trial (serum beta-2 microglobulin and ECOG PS). This study concludes that monthly infusions of Aredia significantly reduce skeletal complications of multiple myeloma.

"Our studies show that Aredia is a safe and generally well tolerated therapy for the treatment of osteolytic bone lesions of multiple myeloma," noted Berenson. "Multiple myeloma osteolytic bone lesions severely damage the bones which may lead to extreme pain, fractures and spinal cord compression. Until now, we have had to rely on radiation, chemotherapy, surgery and narcotics to treat the skeletal complications of this disease. This therapy is good news for both the physicians and the patients who are struggling with the skeletal complications of this deadly cancer."

Berenson's 21-month data further support evidence he presented at ASH last year regarding the first part of this study, a 9-month multicenter, double-blind, placebo-controlled Phase III clinical trial in which 377 evaluable patients were randomized to receive either 90mg/month of Aredia or placebo in addition to their antimyeloma chemotherapy regimen. The results demonstrated that 41 percent of patients receiving placebo developed a skeletal complication (fractures, local irradiation, spinal compression, and/or surgery) compared to 24 percent in those taking Aredia.

Fewer Aredia-treated patients suffered any pathologic fractures (P=.004) or needed any radiation to bone (P=.049). In addition, decreases in pain scores (a secondary variable) from baseline occurred at endpoint for the Aredia-treated patients with pain at baseline (P=.026). The statistical significance of analyses of these secondary endpoints of pain, quality of life, and performance status may be overestimated since numerous analyses were performed.

The most common adverse experiences, regardless of drug relationship, were fever, anemia, nausea, upper respiratory tract infection, and fatigue. When Aredia is prescribed, serum calcium and electrolytes must be monitored closely, as must patients with pre-existing anemia, leukopenia, thrombocytopenia. Aredia should not be used to treat patients with clinically significant hypersensitivity to Aredia or other bisphosphonates.

Aredia was first marketed in 1991. The results of this 9-month study led the FDA to clear Aredia for marketing in September 1995 for the treatment of patients with osteolytic bone lesions of multiple myeloma in conjunction with standard antimyeloma chemotherapy. Aredia is believed to work by inhibiting bone resorption without inhibiting bone formation and mineralization. Developed and manufactured by Ciba Pharmaceuticals, Aredia is marketed exclusively in the United States by the Chiron Therapeutics business unit of Chiron Corp.

Multiple Myeloma is a cancer characterized by the proliferation of malignant plasma cells in the bone marrow which, in more than two-thirds of patients, results in skeletal complications such as fractures due to progressive irreversible bone destruction. In the United States, there are an estimated 50,000 people living with multiple myeloma and approximately 13,000 newly diagnosed cases each year. The American Cancer Society estimates multiple myeloma will result in approximately 10,000 deaths in 1995. In addition to Aredia, multiple myeloma traditionally has been treated with chemotherapy, radiotherapy, narcotics and surgery. For more information and a package insert on Aredia, please call Chiron Professional Services at 800/CHIRON-8, selection No. 2.

Ciba Pharmaceuticals is a division of Ciba-Geigy Corp. of Tarrytown, N.Y., a wholly owned subsidiary of Ciba-Geigy Limited of Basel, Switzerland. Ciba is a leading developer and manufacturer of healthcare and agricultural products and specialty 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.

Chiron Corp. is a biotechnology company headquartered in Emeryville, Calif., near San Francisco. Chiron is building a healthcare business that addresses needs in several markets: diagnostics, including immunodiagnostics and bDNA probe assays; vaccines, emphasizing adult and pediatric infectious diseases; therapeutics, with an emphasis on oncology, neurology, endocrinology and serious infectious and other diseases requiring critical care; and ophthalmic products for the surgical correction of vision. Additional research programs are underway in gene therapy and gene transfer, and cardiovascular disease.

CONTACT: Chiron Corp.

Larry Kurtz, 510/601-2476

Kimberly Kraemer, 510/601-2412