HONOLULU--(BUSINESS WIRE)--Twelve month results from a Phase IIB study with odanacatib, (formerly MK-0822), an investigational selective inhibitor of cathespin-K, demonstrated dose-dependent increases in bone mineral density (BMD) at key fracture sites, and reduced bone turnover compared to placebo in postmenopausal women with low BMD when given at doses of 10, 25 or 50 mg. These findings were presented today at the 29th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR).
In this study, treatment with odanacatib 50 mg once-weekly (n =77) significantly increased lumbar spine (LS) BMD at 12 months by 3.4 percent compared to baseline values while treatment with placebo (n=81) decreased LS BMD by 0.1 percent compared to baseline. Dose-related increases in BMD at all other measured skeletal sites were seen with the 10, 25 and 50 mg doses of odanacatib compared to baseline, but not at the 3 mg dose or placebo. The study also explored biochemical markers of bone turnover. The 50 mg dose reduced sCTx (serum C-telopeptides of Type 1 collagen) - a biochemical marker of the rate of bone removal - by 57 percent from baseline and minimally reduced s-BSAP (bone specific alkaline phosphatase), a measure of the amount of new bone being formed, by 18 percent (s-CTX and s-BSAP for placebo = - 0.6 percent and - 3 percent respectively).
“The favorable effects on bone mineral density seen with odanacatib in this study are encouraging,” said Dr. Henry Bone, lead investigator and director of the Michigan Bone and Mineral Clinic in Detroit, Michigan. “It is a promising investigational drug being studied for the treatment of osteoporosis. We look forward to the results of further trials.”
Odanacatib, an investigational compound which is being developed for the treatment of osteoporosis, is a highly selective inhibitor of the cathepsin K enzyme. The cathepsin K enzyme is believed to play a role in both osteoclastic bone resorption and in degrading the protein component of bone. The inhibition of the cathespin K enzyme by the investigational compound odanacatib is a mechanism of action different from that of currently approved treatments such as the bisphosphonates.
Phase III studies with odanacatib are being initiated.
Odanacatib increased BMD
These findings are from a multi-center, double-blind, randomized, placebo-controlled study in postmenopausal women with low BMD. The study evaluated 399 postmenopausal women with BMD T-scores less than -2.0 but greater than -3.5 who were randomized to odanacatib 3, 10, 25 or 50 mg administered orally once-weekly without regard to food or placebo for 12 months, with a planned 12 month follow up. The follow-up period is currently ongoing.
BMD reflects the amount of mineralized bone tissue in a certain volume of bone, and correlates with the strength of bones and with their resistance to fracture. A BMD test is used to measure bone density and to help determine fracture risk.
The primary study endpoint was change in BMD at the lumbar spine. Secondary endpoints included change in BMD at other skeletal sites (total hip, femoral neck, hip trochanter, total body and distal forearm), and change in biochemical markers of bone turnover. Results at 12 months showed the following:
Percent Increase In BMD From Baseline Dose/Once-weekly Lumbar Total hip Femoral Hip for 12 Months Spine Neck trochanter --------------------- ----------- ----------- ----------- ------------ Odanacatib 10 mg (n=77) 1.5% 1.1% 0.7% 1.7% --------------------- ----------- ----------- ----------- ------------ Odanacatib 25 mg (n=78) 2.7% 1.5% 1.8% 1.9% --------------------- ----------- ----------- ----------- ------------ Odanacatib 50 mg (n=77) 3.4% 1.9% 2.5% 2.2% --------------------- ----------- ----------- ----------- ------------ Placebo (n=81) -0.1% -0.6% -0.1% -0.7% --------------------- ----------- ----------- ----------- ------------
Increases in BMD with odanacatib 3 mg were not observed. Increases in total body and distal forearm BMD were not observed at the four odanacatib doses studied. Reduction in bone turnover from baseline as measured by sCTx was 57 percent with odanacatib 50 mg, 36 percent with odanacatib 25 mg and 22 percent with odanacatib 10 mg. Reduction in bone turnover was not observed with either odanacatib 3 mg or placebo.
The discontinuation rates due to an AE for the four doses of odanacatib were similar to placebo. There were 5.1 percent of patients who discontinued due to AEs in the 50 mg odanacatib group compared to 10.8 percent of those receiving placebo. Skin disorders were reported in 20.5 percent of patients receiving 50 mg of odanacatib and in 18.1 percent of those receiving placebo.
The study was conducted in North America, South America, Europe, Australia and New Zealand.
About osteoporosis
Osteoporosis, a disease in which the density and quality of bone are reduced, affects over 75 million people in the U.S., Europe, South America and Japan. As bones become more porous and fragile, the risk of fracture is greatly increased. The most common fractures associated with osteoporosis occur at the hip, spine and wrist and the risk of having an osteoporosis-related fracture increases with age. In fact, one in three women over age 50 will experience osteoporotic fractures, as will one in five men. According to the International Osteoporosis Foundation (IOF), the worldwide incidence of hip fracture is projected to increase by 240 percent in women and 310 percent in men by 2050.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck 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 Merck 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.
Forward-looking statement
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management’s current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck’s business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck’s Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.
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Source: Merck & Co., Inc.
