Blockbuster Osteoporosis Drug Moves Towards FDA Approval

Denosumab, a ground-breaking osteoporosis drug that’s been moving through clinical trials for several years, is set to take the first step towards FDA approval this week.

An advisory panel will meet Thursday to make recommendations as to whether denosumab, which will be marketed under the brand name Prolia, should be approved for the treatment of osteoporosis in postmenopausal women. The FDA will make the final decision on October 19, and usually follows the recommendations of its advisory panel – although another osteoporosis drug backed by an advisory panel last year, Fablyn, has yet to gain FDA approval.

How does denosumab differ from the usual osteoporosis drugs we currently choose among, e.g., Boniva, Fosamax, and Actonel?

It’s not a bisphosphonate, which means it works differently. Most important to the end user, it doesn’t come with the array of potential gastrointestinal side effects that bisphosphonates carry. While bisphosphonates are usually taken orally, denosumab would be a twice-yearly injection.

And how does it work? Denosumab helps prevent bone loss by blocking a particular protein that controls the production of osteoclasts. Osteoclasts are the “bad” cells, the ones that break down (“remodel”) your bones; their counterpart, osteoblasts, help build bone. 

The results of a final phase III clinical trial, posted in February on a National Institutes of Health Web site, pubmed.gov, states that “Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.” Alendronate is the generic name for Fosamax.

A total of 11,000 patients participated in six different phase III trials leading up to this week’s first step towards approval. Overall, denosumab reduced risk of spinal fracture by 70%. However, potential side effects include a risk of serious skin infection, and cataracts. As part of its work this week, the advisory panel will discuss what kind of warnings potential recipients should be given about denosumab's side effects.

Denosumab is produced by Amgen Inc. of Thousand Oaks, Cal., the world’s largest biotech company. Wall Street analysts, closely tracking Amgen’s stock as the drug moves towards approval, say it could generate $2 billion in yearly sales for Amgen – nearly 25% of the $8.7 billion annual market for osteoporosis drugs.

The cost of the drug to patients would be $850-$1200 a year, similar to that of bisphosphonates.

Amgen is concurrently seeking FDA approval for another usage for denosumab: as a treatment for hormone therapy-induced bone loss in breast and prostate cancer patients.

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In other breaking news, the first of three “bellwether” lawsuits involving Fosamax gets underway in New York this week. U.S. District Judge John Keenan will preside over the trial, which is a consolidation of some 700 separate lawsuits against Merck & Co., manufacturer of Fosamax.