Phase 2 Study of Patients Previously Treated with IV Bisphosphonates Showed Denosumab Reduced Bone Resorption and Skeletal-Related Events
Comparison of Phase 2 Studies Showed Consistent Reduction of Bone Resorption with Denosumab in either Bisphosphonate-Naive or -Treated Patients
Sub-group Analysis of Phase 3 Study Showed Denosumab Increased Bone Mineral Density Throughout the Skeleton In Women With Non-Metastatic Breast Cancer Receiving Aromatase Inhibitor Treatment
ABSTRACT NUMBERS: 9574, 3596, and 546
CHICAGO--(BUSINESS WIRE)--May 31, 2008--Amgen (NASDAQ: AMGN) today announced results from three denosumab studies in cancer patients. A Phase 2 study of metastatic patients previously treated with IV bisphosphonates found that denosumab normalized a key marker of bone resorption at a significantly greater rate than that seen with continuation of IV bisphosphonates, and also patients receiving denosumab experienced fewer skeletal-related events (SREs). A separate retrospective analysis comparing the results of this study to another Phase 2 study of patients never treated with an IV bisphosphonate revealed that the effect of denosumab on bone turnover markers was similar regardless of previous exposure to bisphosphonates. In addition, a sub-analysis of a Phase 3 trial in an earlier-stage cancer population of non-metastatic breast cancer patients showed that denosumab increased bone mineral density (BMD) at all sites measured, including cortical bone. These results were presented at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO).
Phase 2 Data of Patients Previously Treated with IV Bisphosphonates
The study evaluated patients whose urinary N-telopeptide (uNTx) levels had not normalized despite treatment with IV bisphosphonates. The primary endpoint of patients with uNTx less than 50 at week 13 was achieved by 71 percent of patients in the denosumab arms compared with 29 percent in the IV bisphosphonate arm (p less than 0.001). In addition, denosumab induced suppression of uNTx levels faster than IV bisphosphonate (9 days versus 65 days, respectively).
At week 25, denosumab treatment was associated with fewer on-study SREs (8 percent) than were seen in those receiving IV bisphosphonate therapy (20 percent). Skeletal-related events include fractures, radiation or surgery to bone, and spinal cord compression.
The adverse event profile of denosumab was similar to that of advanced cancer patients receiving treatment, and balanced across treatment arms. The most common adverse events included bone pain, nausea, anemia, constipation, and asthenia. No neutralizing anti-denosumab antibodies were observed.
"Skeletal-related events can be a devastating complication of bone metastases," said Karim Fizazi, M.D., Ph.D., Head of the Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, France. "Elevated markers of bone resorption are routinely accepted indicators of poor outcomes for our advanced cancer patients. So it was encouraging to see that in this study, denosumab was able to further suppress bone turnover in patients previously on bisphosphonates, and that denosumab patients also reported fewer skeletal-related events."
Comparison of Phase 2 Data on Bone Turnover Markers of IV Bisphosphonate-Treated Versus Bisphosphonate-Naive Patients
In a comparison of the effect of denosumab on bone turnover markers in two Phase 2 trials, one trial involving patients previously treated with IV bisphosphonates versus a second trial involving patients not previously treated, denosumab was found to suppress bone resorption to a similar extent, regardless of prior bisphosphonate exposure. This side-by-side comparison of changes in serum-C telopeptide (sCTx), a marker of bone breakdown, from baseline to week 25, showed that at the six months time point, denosumab suppressed bone resorption by 85 percent in bisphosphonate-naive patients compared with 80 percent in patients with prior exposure to IV bisphosphonates. In patients previously treated with IV bisphosphonates, denosumab suppressed bone resorption by 80 percent compared with 45 percent in patients who continued on IV bisphosphonates.
In this comparison, the incidence of serious adverse events was similar across treatment groups in both studies. Types of adverse events were consistent with a population of patients with advanced cancer, and patients treated with IV bisphosphonates. The most common adverse events across all treatment arms were arthralgia, bone pain, asthenia, and nausea.
Phase 3 Sub-Group Analysis of BMD in Women With Non-Metastatic Breast Cancer Undergoing Aromatase Inhibitor Treatment
Sub-group analysis results of a Phase 3 pivotal study also presented at ASCO showed denosumab increased BMD at all skeletal sites measured, including in highly cortical sites, in non-metastatic breast cancer patients receiving adjuvant aromatase inhibitor (AI) therapy. The new analysis showed consistent increased BMD at the lumbar spine, total hip, femoral neck, and distal 1/3 radius at 12 months, regardless of duration or type of AI therapy, prior tamoxifen use, age, body mass index, or baseline T-score. The sub-group analysis findings presented at ASCO remain consistent with the efficacy and safety findings presented at the 2007 San Antonio Breast Cancer Symposium (SABCS).
In this study, overall rates of adverse events were similar to those seen with placebo (91 percent denosumab versus 90 percent placebo). The most common adverse events, consistent with adverse events usually associated with AI therapy, were arthralgia, pain in extremity, back pain, and fatigue.
"Because denosumab specifically targets RANK Ligand, we believe it works in a different way from other bone loss and destruction treatments," said Roger Dansey, M.D., Global Development Leader for Denosumab Oncology at Amgen. "Results from the denosumab oncology program presented thus far are encouraging and we look forward to results from additional clinical trials in the bone loss and SRE settings."
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. The denosumab oncology program has a specific commitment in prostate cancer, studying more than 4,300 patients to determine the treatment effect of denosumab to treat and prevent bone loss, treat and prevent SREs and delay bone metastases in men with 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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