Merck & Co has decided to discontinue development of its osteoporosis candidate odanacatib after seeing an elevated risk of stroke in studies.
The decision to drop the once-weekly cathepsin K inhibitor marks the end of a long and arduous development path for odanacatib, which had once been held up as a potential $3bn-a-year blockbuster for Merck.
The company prematurely halted a phase III trial of the drug in 2012 after seeing a clear benefit on fractures rates in postmenopausal women with osteoporosis, although it did note at the time that safety issues remained “in certain selected areas”. It announced a delay in the programme early in 2013.
Now the company has confirmed it does not intend to seek regulatory approval for odanacatib, with R&D chief Roger Perlmutter saying: “We believe that the increased risk of stroke in our phase III trial does not support further development.”
The decision raises further questions about the future of cathepsin K inhibitors, a class marked by a string of failures in the clinic, and whether the stroke risk is a class effect or something linked to Merck’s molecule.
Ono Pharmaceutical was also developing a drug in the class called ONO-5334 but pulled the programme in 2012 without giving reasons for the decision, while Medivir discontinued its MIV 701 in 2009 and Novartis dropped its balicatib candidate in 2006 after it was found to cause skin lesions.
Meanwhile, the decision to take odanacatib out of the running is a boost for UCB and Amgen, who are developing an osteoporosis drug that has been viewed as a close rival to Merck’s drug.
Their anti-sclerostin antibody romosozumab is well ahead of other drugs in the emerging class and has been shown to be superior to Eli Lilly’s big-selling osteoporosis therapy Forteo (teriparatide) in phase III trials.
Romosozumab was filed for approval in the US in July based on the results of the 7,200-patient FRAME study, which showed the drug reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis compared to placebo.
Meanwhile, the demise of odanacatib could also benefit Radius Health’s new parathyroid hormone (PTH) based candidate abaloparatide.
Deutsche Bank analysts have said they see romosozumab and abaloparatide dominating the market for drugs that boost bone formation in osteoporosis in the coming years with sales well above $1bn.