Odanacatib, Merck's Investigational Cathepsin K Inhibitor, Reduced Markers of Bone Turnover in Women with Breast Cancer and Bone Metastases

Results from a new Phase II study showed oral odanacatib (MK-0822), Merck & Co., Inc.'s investigational selective cathepsin K inhibitor, reduced measures of bone turnover (breakdown and rebuilding of bone) in women with breast cancer that has spread to the bones (bone metastases). These results will be presented on June 3 at the 2008 American Society of Clinical Oncology (ASCO) annual meeting (Poster #4, Abstract #1023). "Bone metastases represent a frequent and serious complication for patients with breast cancer,” said Christopher Wynne, M.B., CH.B., study investigator and clinical oncologist, Christchurch Clinical Studies Trust, New Zealand. "These findings show that odanacatib reduced several well characterized biochemical markers of bone turnover in cancer patients with metastasis to bone, indicating this investigational medicine has the potential to slow the accelerated rate of bone destruction associated with bone metastases.” Odanacatib is a highly selective, potent inhibitor of the cathepsin K enzyme. Cathepsin K enzyme plays a key role in breaking down the protein in bone. In cancer that has spread to the bones, tumor cells speed up the normal process of bone breakdown and formation, which in turn results in further tumor growth and bone destruction. By inhibiting cathepsin K activity, odanacatib represents a potential novel therapeutic approach for metastatic bone disease that works differently from other commonly used medicines. In this study, treatment with oral odanacatib 5 mg once daily (n=29) reduced the level of urinary N-telopeptide (uNTx), a commonly used marker of bone resorption (breakdown), by 77 percent from baseline levels over four weeks. These results were seen as early as day seven, the first measurement point. Treatment with intravenous zoledronic acid 4 mg (n=14) reduced uNTx by 73 percent. In addition, decreases in other markers of bone turnover, including the marker of bone resorption urinary deoxpyridinoline (uDPD) and the marker of bone formation serum bone-specific alkaline phosphatase (sBSAP) were observed with odanacatib; as was an increase in serum crosslinked C-terminal peptide (s1CTP), a marker of cathepsin K activity. In this study, the most common clinical adverse events reported included nausea, vomiting, headache and bone pain. Two patients in the odanacatib group experienced mild skin adverse events (rash and pruritis), both of which resolved within one week without discontinuation of study medication. Decreased lymphocyte count was the most common laboratory adverse event in both treatment groups. This randomized, double-blind, multicenter study included 43 women with breast cancer and metastatic bone disease who received oral odanacatib 5 mg daily or intravenous zoledronic acid 4 mg on Day 1. The mean age of women was 60 years. The primary endpoints of the study were the marker of bone resorption urinary N-telopeptide of type I collagen corrected for creatinine (uNTx; pmol BCE/µmol creatinine) and safety. "This is the first study to evaluate odanacatib in cancer patients," said Antonio Lombardi, M.D., senior director, Merck Research Laboratories. "Based on these findings, larger Phase III studies using the 5 mg daily dose of odanacatib are being planned for patients with breast and prostate cancer." A Phase III trial evaluating odanacatib for the treatment of osteoporosis in postmenopausal women also is underway. About bone metastases Metastatic bone disease occurs when cancer cells from the primary tumor spread to the bone. Bone is the most common site for cancer to spread in patients with breast cancer. Up to three-quarters of women with advanced breast cancer are affected and two-thirds of these women develop skeletal-related events or serious complications, such as excruciating pain, bone loss leading to fractures, nerve damage including spinal cord compression, surgery or radiation therapy for bone complications or dangerously high levels of calcium in the blood (hypercalcemia). New data on other investigational Merck oncology medicines also featured During this year's meeting, a range of new data with Merck's oncology portfolio will be featured, covering a variety of therapies and investigational medicines. Among those to be highlighted during an oral session on June 1 are results from two Phase I trials with MK-0646, an investigational monoclonal antibody targeting the insulin-like growth factor receptor 1 (IGF1R), (Abstracts #3519 and #3520) being developed in collaboration with Pierre Fabre Medicament. These first-in-man studies evaluated safety and tolerability, optimal dose and early clinical activity of MK-0646 in patients with advanced solid tumors. Based on these findings, Phase II trials have been initiated with MK-0646 in combination with chemotherapy in patients with metastatic colon cancer and in patients with non-small cell lung cancer. Commitment to oncology research Merck is committed to all aspects of cancer care – prevention, treatment and supportive care. Through strong internal research capabilities, selective alliances and acquisitions, and enabling technologies such as the molecular profiling platform of Rosetta, Merck is looking to lead in the discovery, development and delivery of targeted anticancer therapies customized for patient subpopulations. About Merck Merck & Co., Inc., is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate its medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com. 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