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Results Reported for Odanacatib in Women With Postmenopausal Osteoporosis
Bone mineral density significantly improved versus placebo (Oct. 15)
Positive results from a phase II trial of odanacatib (Merck), an investigational cathepsin K (cat-K) inhibitor in development for the treatment of osteoporosis in postmenopausal women, were recently presented at the 34th Annual Meeting of the American Society for Bone and Mineral Research.
In the randomized, double-blind, placebo-controlled study, treatment with odanacatib 50 mg once weekly significantly increased bone mineral density (BMD) compared with placebo over a 2-year period in postmenopausal osteoporotic women who had received 3 or more years of treatment with alendronate. Patients were allowed to have been off alendronate therapy for up to 3 months immediately prior to enrollment in the study.
Participants were at least 60 years of age with low BMD T-scores (less than or equal to –2.5 and greater than –3.5) at any hip site (femoral neck, trochanter, or total hip) without a history of fragility fracture, or with BMD T-scores less than or equal to –1.5 and greater than –3.5 at any hip site, with a history of fragility fracture (except hip fracture). The patients were randomly assigned to receive odanacatib 50 mg once weekly or placebo for 24 months. All of the patients received vitamin D3 (5,600 IU/week) and calcium supplementation, if needed.
In the odanacatib group, BMD changes from baseline at 24 months were significantly different versus placebo at all three hip sites (+1.73%, +1.83%, and +0.83% for the femoral neck, hip trochanter, and total hip, respectively, vs. –0.94%, –1.35%, –1.87% with placebo), and the lumbar spine (+2.28% vs. –0.30% change with placebo). At the distal forearm, BMD changes from baseline at 24 months were –0.92% and –1.14%. The difference versus placebo at the distal forearm (+0.22%) was not statistically significant.
Treatment discontinuation rates due to adverse events were 9.0% for patients receiving odanacatib and 3.3% for patients receiving placebo. The most common clinical adverse events in patients receiving odanacatib and placebo, respectively, were urinary-tract infections (11.5% vs. 16.5%), back pain (11.5% vs. 9.9%), arthralgia (9.0% vs. 9.9%), fractures (4.9% vs. 13.2%), bronchitis (5.7% vs. 4.1%), nasal pharyngitis (3.3% vs. 5.8%), and upper respiratory infection (4.1% vs. 0.8%).
In osteoporosis, bone loss occurs because the rate of bone resorption exceeds that of bone formation.Osteoclasts (cells that resorb bone) secrete signaling factors to stimulate osteoblasts (cells that form bone). Odanacatib selectively inhibits cat-K, the primary enzyme in osteoclasts that digests proteins during bone resorption.
Source: Merck, October 15, 2012.