ROCKVILLE, Maryland—Amgen's potential blockbuster osteoporosis drug denosumab (Prolia) was targeted for October 19 FDA approval, but Dow Jones reports that analysts are now expecting a delay of 3 months as the agency wrestles with safety concerns. Part of the concern relates to denosumab's mechanism. Unlike other osteoporosis drugs on the market, denosumab blocks RANKL (RANK ligand), a signaling protein that mediates bone removal. Denosumab essentially mimics the endogenous effects of osteoprotegerin, which counterbalances RANKL in healthy bone.

The fact that, aside from vaccines, denosumab would be the first biologic to be marketed to primary care physicians rather than mainly to specialists may have heightened the regulatory reviewers' caution.

Denosumab approval is virtually certain, in view of the strong supporting data from 6 Phase III trials. However, a 90-day delay, which could push approval into next year, would have serious consequences on the company's launch expectations and 2010 sales projections.

Denosumab is expected to be a big seller for Amgen because it can be taken just twice a year as subcutaneous injections and because it will present an option for osteoporosis patients who cannot tolerate bisphosphonates. Even if denosumab wins only 16% of the US osteoporosis market, sales will be an estimated $1.3 billion.

Cancer-related bone loss is likely to add even more sales, and Amgen is expected to file for that indication in 2010.

According to Thomas Gryta, writing for Dow Jones Newswires, “…denosumab has reinvigorated Amgen's stock by driving it up 31% since hitting a 52-week low in April. But long-term investors may be hoping for more as the shares hit an all-time high of $86.92 in September 2005 and first crossed the $60 mark almost ten years ago.”