Merck & Co has now pulled the plug on its troubled late-stage osteoporosis candidate odanacatib after concluding that the drug's benefit does not outweigh its risks.
The decision - which follows a number of setbacks for the drug in recent years - comes after an independent analysis confirmed reports of an increased risk of stroke in postmenopausal women taking the cathepsin K inhibitor.
"We are disappointed that the overall benefit-risk profile for odanacatib does not support filing or further development," said Roger Perlmutter, president of Merck Research Laboratories.
"We have learned that odanacatib treatment reduces the risk of osteoporotic fractures. At the same time, we believe that the increased risk of stroke in our Phase III trial does not support further development."
In osteoporosis, bone loss occurs because of an imbalance in the rate of bone resorption versus bone formation. Osteoclasts, cells that resorb bone, secrete signalling factors to stimulate osteoblasts, cells that form bone. Odanacatib works by selectively inhibiting cathepsin K, the primary enzyme in the osteoclasts that digests proteins during bone resorption, and has been shown in trials to incude progressive increases in BMD.
According to data from the LOFT trial, odanacatib significantly cut the risk of three types of osteoporotic fractures compared to placebo, and also reduced the risk of the secondary endpoint of clinical vertebral fractures, and the firm had been planning on submitting marketing applications in the US and Japan last year.
Data from the new analysis of major cardiovascular events will be presented in September at the American Society for Bone Mineral Research, the firm noted.