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Interim Phase 2 Results of Open-Label Clinical Trial of Denosumab in Giant Cell Tumor of Bone Demonstrated 87 Percent Response Rate
Giant Cell Tumor is a Rare Bone Tumor Afflicting Younger Adults For Which Few Treatment Options Exist ABSTRACT NUMBER: 10500CHICAGO, May 31, 2008 (BUSINESS WIRE) -- Amgen (NASDAQ:AMGN) today announced interim results of an open-label Phase 2 study demonstrating a positive response rate to administration of denosumab in subjects with recurrent or unresectable giant cell tumor of bone. The study was presented at the 2008 American Society of Clinical Oncology (ASCO) annual meeting.
Interim results from the twelve-month, open-label Phase 2 study show that 120 mg of denosumab, administered subcutaneously once monthly with a loading dose at days 8 and 15 of month one, met the primary and all secondary endpoints. The primary endpoint was tumor response (elimination of greater than or equal to 90 percent of giant cells or no radiographic progression of the target lesion). Out of 35 patients enrolled in the study, 25 were eligible for this interim analysis, with 24 receiving denosumab and 15 being eligible for efficacy analysis based on availability of pre- and post-radiology and histology assessments. Thirteen of 15 patients (87 percent) had tumor response to denosumab treatment. Of those, 9 of 9 had a histologic response which showed almost complete or complete elimination of giant cells. In addition, 4 of 6 patients had a radiographic response demonstrating no further progression. The two patients who did not meet radiographic response criteria were considered stable by investigators. Three subjects reported evidence of new bone formation and repair visible by radiology.
"Denosumab has shown profound effect in this small group of subjects" said David Thomas, FRACP, Ph.D., Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. "For researchers in this field and our patients this represents an important advance in the understanding of potential treatment approaches for this rare disease."
Other observations included: reduction in activity on PET scan, stabilization of tumors within the bone, reduction in soft tissue expansion outside the bone, and evidence of new bone formation and repair. Some subjects had improvement in function evidenced by reduction in pain, improved mobility, and in some cases, return to work.
In this study, denosumab appeared generally well-tolerated. The most frequent adverse events reported were headache (3 (13 percent)) and nasopharyngitis (3 (13 percent)). No treatment-related serious adverse events related to denosumab or deaths were reported, and no neutralizing anti-denosumab antibodies were observed.
Giant cell tumor of bone is rich in RANK Ligand positive cells, which results in giant osteoclasts that destroy the bone locally.
"Giant cell tumor patients have limited treatment options, so we are very encouraged by these results," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "These data also support the scientific view that RANK Ligand may play a key role in bone loss and destruction, including in advanced cancer, where denosumab is being studied in breast, prostate, and other solid tumors."
About Giant Cell Tumor
Giant cell tumor of bone is a locally aggressive, benign tumor afflicting younger adults between the ages 20 to 40. Approximately 800 new giant cell tumor of bone cases are identified in the United States each year, which account for about one fifth of all benign primary bone tumors.
Most tumors occur in the long bones of the body, often around joints, but can spread to the lung. Patients can experience severe bone pain, swelling, loss of mobility if the tumor is close to a joint, and pathologic fracture. Giant cell tumors are slow growing, but have a 20 percent recurrence rate within three years of onset. When tumors recur, they become more likely to spread to other parts of the body. Currently, treatment options are very limited. The primary option is surgery, which may include joint replacement and amputation.
About Denosumab and Amgen's Research in Bone Biology
Denosumab is the first fully human monoclonal antibody in late-stage clinical development that specifically targets RANK Ligand, the essential regulator of osteoclasts (the cells that break down bone). With more than 19,000 patients participating in trials across indications worldwide, the denosumab development program is the largest ever initiated by Amgen. This broad and deep development program demonstrates Amgen's commitment to researching and delivering pioneering medicines to patients with unmet medical needs. Amgen is studying denosumab in numerous tumor types across the spectrum of cancer induced bone disease. Over 11,000 patients are currently enrolled in denosumab oncology clinical trials testing the drug for bone loss associated with cancer treatment-induced bone loss in breast and prostate cancers, for the prevention of skeletal related events due to the spread of cancer to the bone in multiple myeloma and multiple solid tumors, and for its potential to delay bone metastases in prostate cancer.
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
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