Odanacatib effective for osteoporosis in mid-stage trial

OsteoporosisNew results from a 4-year mid-stage trial of Merck’s osteoporosis drug Odanacatib (codenamed MK-0822) were presented at the American Society for Bone and Mineral Research 2010 Annual Meeting in Toronto, Canada.

The data from clinical and preclinical studies, presented in two oral presentations and six posters, provided further background on the potential of odanacatib to increase bone mineral density, cortical thickness and bone strength when treating osteoporosis.

Investigators reported that continuous treatment with odanacatib, an investigational cathepsin-K inhibitor developed by Merck progressively increases hip and spine bone mineral density (BMD) and reduces markers of bone resorption in post-menopausal women with low BMD.

“We are pleased to be able to have such a robust presentation of new data for odanacatib at the 2010 ASBMR Annual Meeting,” said Albert Leung, M.D., Ph.D., executive director, Clinical Research, Merck Research Laboratories. “The clinical and preclinical data being presented show long-term increase in bone mineral density and impact on bone formation with odanacatib therapy. We are continuing our strong and long-standing commitment to the field of osteoporosis with a large and rigorous Phase III program to evaluate the long-term efficacy and safety of odanacatib.”

Dr Neil C. Binkley, MD, an investigator from the University of Wisconsin–Madison, said, “Women who received 50 mg of odanacatib at some point in the study increased their spine BMD from 5.6% up to roughly 10%; those who were on the less effective doses had a less robust effect, increasing their BMD by about 3.1%,”

However, he added that as soon as odanacatib is stopped, BMD levels quickly revert to their baseline levels, and markers of bone remodeling rapidly increase.

Odanacatib selectively inhibits the cathepsin-K enzyme. It is this selectivity that makes the drug safer than previous cathepsin-K inhibitors. No episodes of skin disorders, scleroderma, or morphea-like lesions, which have been reported with other agents in this class, occurred, according to the new data.

“The numbers are very small, so all of these data must be interpreted in this light,” Binkley said. “However, at this point, we are optimistic and believe that this agent will be another option for the management of osteoporosis.”

Odanacatib acts through selectively inhibition of cathepsin-K, which is known to play a central role in the function of osteoclasts. Osteoclasts are cells that break down existing bone tissue, particularly the protein components of bone. Inhibition of cathepsin-K is a novel approach to the treatment of osteoporosis.

As the safety issues of osteoporosis treatment with bisphosphonates are under investigation, any new approach to treat osteoporosis, a major public health threat which afflicts 55% of Americans aged 50 and above, would draw great attention from the pharmaceutical industry.