Pivotal Phase 3 Data Show Denosumab Increased Bone Density Throughout Skeleton in Non-Metastatic Breast Cancer Patients on Adjuvant Aromatase Inhibitor Therapy

Update: Prolia (denosumab) Now FDA Approved - June 1, 2010
SAN ANTONIO--(BUSINESS WIRE)--Dec 15, 2007 - Amgen (NASDAQ:AMGN) today announced results of the first Phase 3 pivotal study to complete in the denosumab oncology development program. The study evaluated denosumab's effect on bone density across the skeleton in women with non-metastatic breast cancer who were receiving adjuvant Aromatase Inhibitor (AI) Therapy. These results were presented during the Late Breaking Session at this year's 30th Annual San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.

Results from the Phase 3 HALT Breast Cancer 135 study show that denosumab, a fully human monoclonal antibody under investigation as a twice yearly subcutaneous injection, increased bone density worsened by AI therapy, including in highly cortical areas of the skeleton. In addition to increasing bone mineral density (BMD) of the trabecular bone (spongy bone matrix), denosumab showed increases in cortical bone, the dense outer shell of the skeleton which is responsible for the supportive and protective function of the skeleton.

"The risk of bone loss for women with breast cancer is a genuine concern and needs to be proactively managed when treating with aromatase inhibitors," said Georgiana Kehr Ellis, M.D., Associate Professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine, Seattle, WA. "In this study, denosumab data looks promising, and as a clinician, I look forward to having a potential alternative to existing therapies."

Skeletal integrity is normally maintained through complex biological processes that carefully regulate the bone remodeling process. However, disruption of these processes with AI therapy in postmenopausal breast cancer patients, already in a state of accelerated bone loss, can lead to worsening imbalances in bone resorption and formation. Bone loss can occur with over stimulation of osteoclasts; the cells responsible for bone resorption. Too much resorption causes progressive bone loss and weakens cortical and trabecular bone throughout the skeleton. RANK Ligand inhibition is being investigated for the clinical potential to both prevent bone resorption and halt active bone destruction.

The Phase 3 data show that lumbar spine BMD increased significantly at all time points with the denosumab group (n=127) as early as one month. At month 12 (primary endpoint) a 5.5 percent (p less than 0.0001) difference from placebo (n=125) was observed. Additionally, a consistent effect of denosumab was demonstrated on the Total Hip BMD (3.7 percent difference from placebo) and Femoral Neck BMD (2.5 percent difference from placebo) at 12 months (secondary endpoints).

In addition, exploratory endpoints evaluated the effect of denosumab at the distal radius and on total body. A 3.8 percent change in BMD at the distal radius was observed at month 12 with denosumab compared to placebo and at 24 months that difference increased to 6.1 percent. A 3 percent increase in BMD on Total Body was shown at month 12 with denosumab compared to placebo and at 24 months BMD in the denosumab arm increased to 4.2 percent compared to placebo.

In the study, denosumab was generally well tolerated, with overall rates of adverse events similar to placebo. The most common adverse events (AEs) were consistent with those usually associated with AI therapy, and included, arthralgia, pain in extremity, fatigue, back pain, constipation, cough, and insomnia.

"The results of this pivotal study provide a promising glimpse of the potential of denosumab to help manage bone disease in multiple tumor types and stages of disease in the cancer setting," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "This data on denosumab evaluating its effect on BMD throughout the skeleton, including cortical sites, should be encouraging to clinicians who witness the devastating effects of cancer and cancer treatment on their patients' bones."

About Denosumab

Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, the essential mediator of osteoclasts (the cells that break down bone). Denosumab inhibits all stages of osteoclast activity through a targeted mechanism that does not incorporate into bone matrix. In the oncology setting, denosumab is being investigated in treatment-induced bone loss (in breast cancer and prostate cancer patients) and for its potential to delay bone metastases as well as inhibit and treat bone destruction across many stages of cancer.

About RANK Ligand Inhibition

RANK Ligand is found in all parts of trabecular and cortical bone and RANK Ligand inhibition represents a highly targeted and specific approach to treating osteoclast-mediated bone destruction.

About Amgen in Bone Biology

Amgen is a leader in bone biology and is committed to developing medicines to help the millions of patients with osteoporosis, rheumatoid arthritis and other bone conditions. We have initiated a robust clinical trial program with more than 18,000 patients worldwide to evaluate the benefit/risk profile of denosumab across a number of therapeutic areas. Denosumab is also being studied in a range of bone-loss conditions outside of the oncology setting including postmenopausal osteoporosis and in the treatment of bone erosions in rheumatoid arthritis.

About Amgen

Amgen discovers, develops 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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Posted: December 2007

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