Merck announces results from odanacatib Phase II trial on post-menopausal osteoporosis

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced results from a Phase II trial for odanacatib, an investigational cathepsin K (cat-K) inhibitor in development for the treatment of osteoporosis in post-menopausal women. The results were presented today at the 34^th Annual Meeting of the American Society for Bone and Mineral Research.

In the study, treatment with odanacatib (compared to placebo) significantly increased Bone Mineral Density (BMD) over a two-year period in post-menopausal osteoporotic women who previously had three or more years of treatment with alendronate. Patients were allowed to have been off alendronate therapy for up to three months immediately prior to enrollment in the study.

"Odanacatib works differently than other treatments for osteoporosis by targeting cat-K, a specific enzyme within bone cells," said Albert Leung, M.D., Ph.D., executive director, clinical research, Merck Research Laboratories. "We're excited about these results because understanding the effects of odanacatib in a population of post-menopausal women previously treated for osteoporosis is important to clinicians."

Study evaluated efficacy and safety of odanacatib following treatment with alendronate

This study was a randomized, double-blind, placebo-controlled, multi-center, 24-month trial of odanacatib in 243 women with post-menopausal osteoporosis who had been previously treated with alendronate (dosed daily or weekly) for ≥3 years. Participants were at least 60 years of age with low BMD T-scores (≤-2.5 and >-3.5) at any hip site (femoral neck, trochanter, or total hip) without a history of fragility fracture, or had BMD T-scores ≤-1.5 and > -3.5 at any hip site, with a history of fragility fracture (except hip fracture). The patients were randomized in a 1:1 ratio to receive odanacatib 50 mg once weekly or placebo for 24 months. All patients received vitamin D3 (5600 IU/week) and also calcium supplementation, if needed.

The study evaluated the effects of odanacatib 50 mg once weekly on the following:

• Femoral neck BMD change from baseline compared to placebo over 24 months (primary endpoint)
• Femoral neck BMD compared to baseline over 24 months (key secondary endpoint)
• BMD at hip trochanter, total hip, lumbar spine and distal forearm
• Biochemical markers of bone resorption and formation at months 12 and 24
• Clinical and laboratory assessment of safety and tolerability

BMD was assessed by DXA at baseline, 6, 12 and 24 months. This study was not designed to evaluate the effect of odanacatib on fractures.

Results showed odanacatib significantly increased BMD compared to placebo

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%, +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.

The overall incidence of adverse events, including those that were considered drug-related or serious, were similar between treatment groups. Treatment discontinuations due to adverse events were 9.0 percent for patients receiving odanacatib and 3.3 percent for patients receiving placebo. The most common clinical adverse events in patients receiving odanacatib and placebo, respectively, were urinary tract infection (11.5%, 16.5%), back pain (11.5%, 9.9%), arthralgia (9.0%, 9.9%), fractures (4.9%, 13.2%), bronchitis (5.7%, 4.1%), nasal pharyngitis (3.3%, 5.8%), and upper respiratory infection (4.1%, 0.8%).