Development of odanacatib has been discontinued, and regulatory approval will not be sought.
Merck recently reported that they will stop the development of odanacatib, an investigational cathepsin K inhibitor for the treatment of osteoporosis.
They also will not seek approval for its use, according to a press release. Previously, Merck indicated they planned to submit a New Drug Application to the FDA for the drug.
This conclusion was reached after a phase 3 fracture outcomes study indicated the drug may increase the risk of stroke in postmenopausal women. The Long-Term Odanacatib Fracture Trail (LOFT) investigated the safety and efficacy of the drug in 16,713 postmenopausal women 65-years-old or older.
Patients were randomized to receive either 500-mg per week of odanacatib or a placebo. Patients received vitamin D and calcium if needed, according to Merck.
The drug met its primary endpoints and reduced the risk of hip, spine, and non-vertebral fractures. Adverse events, such as morphea-like skin lesions and atypical femoral fractures, increased in the group taking odanacatib.
Major adverse cardiovascular events were similar between groups, according to Merck. However, more stroke events were reported among patients taking odanacatib.
After an independent adjudication and analysis of cardiovascular events, the increase in stroke risk was confirmed, and Merck decided to discontinue the development of the drug. Data from this analysis will be presented at the American Society for Bone Mineral Research, Merck said.
“We are disappointed that the overall benefit-risk profile for odanacatib does not support filing or further development,” said Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories. “We are very thankful to the researchers and patients who participated in the odanacatib clinical development program. 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 3 trial does not support further development.”