Amgen's BLA submission for denosumab comes ahead of schedule and with the twist of covering multiple indications: treatment and prevention of postmenopausal osteoporosis in women and treatment and prevention of bone loss in patients undergoing hormone ablation for either prostate or breast cancer.

The firm filed the BLA for the RANK ligand inhibitor Dec. 19, giving the compound an Oct. 19, 2009, PDUFA date assuming a standard 10-month review. If the first-in-class agent receives a priority review, the user fee deadline would be June19. Of course, the recent slowdown in the FDA approval process could set the actual approval date back, as could the complications of having parallel reviews for two indications.

Still, Amgen management had indicated during a Nov. 7 analyst meeting that the filing might not be ready until early 2009 (¹ Also see "Aranesp Declines Put More Pressure On Amgen For Denosumab Success" - Pink Sheet, 17 November, 2008., p. 10), so getting the denosumab filing in before the New Year is bound to boost investor sentiment for the firm, which has been pounded by safety, regulatory and payment issues in its blockbuster anemia franchise.

About 11,000 patients have been treated with the fully human monoclonal antibody to date. Six Phase III trials have shown a good safety and tolerability profile, plus efficacy in the ballpark of osteoporosis treatments already on the market. That, plus ease of administration and the possibility of several indications, has made denosumab the darling of new drug candidates among investors (² Also see "Amgen’s Positive Denosumab Pivotal Trial Reduces Overhangs For Firm" - Pink Sheet, 29 July, 2008.).

The BLA is based on two pivotal Phase III trials, in the PMO and prostate cancer settings, that both used fracture endpoints. All six studies, the firm reports, showed denosumab's ability to increase bone mineral density at all skeletal sites measured.

The PMO indication could generate as much as $2.4 billion for Amgen by 2016, according to Deutsche Bank Securities analyst Mark Schoenebaum. He has projected that the drug could have a 10 percent share of the worldwide market for first-line treatment of PMO, a 33 percent share of second-line and 10 percent share for osteoporosis prevention.

Amgen is expected to submit supplemental applications for two other cancer-related indications: treatment of established bone metastases and prevention of bone metastases in patients with earlier stage tumors. Results of a study measuring reduction of skeletal-related events in bone metastases are expected in 2010.

"We expect denosumab to gain significant traction in the cancer market based on favorable safety and dosing," Bernstein analyst Geoffrey Porges said in a Dec. 3 note that projected worldwide oncology sales for the drug could reach "an impressive" $2 billion in 2013.

Amgen CEO Kevin Sharer has said the firm does not plan to seek a U.S. commercialization partner for the drug, which is aimed at the primary care market - not Amgen's specialty of specialty products. The firm estimated it would need about 500 to 1,000 sales reps to cover the PMO prescribing opportunity in the U.S.

The firm also plans to submit marketing applications for denosumab in the first two indications "shortly" in Australia, Canada, EU and Switzerland.

-Pamela Taulbee (p.taulbee@elsevier.com)

Amgen Submits Denosumab BLA Ahead Of Expectations

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