Increased Bone Mineral Density Seen in Phase IIB Study with Odanacatib, Formerly MK-0822, An Investigational Cathepsin K Inhibitor
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: -0-
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.
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.
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Ron Rogers, 908-423-6449
Kim Hamilton, 908-423-6831
Graeme Bell, 908-423-5185
Posted: September 2007