Osteoporosis drug denosumab’s (Prolia) approval delayed in US: Amgen

US FDA has asked Amgen Inc additional information on denosumab (Prolia) in the treatment and prevention of postmenopausal osteoporosis.

Amgen has been issued a Complete Response Letter for the Biologic License Applications (BLA) for denosumab (Prolia) by US FDA.

US FDA requested several items, including further information on the design of Amgen’s previously submitted post-marketing surveillance program.

US FDA, however, did not require additional pre-marketing clinical trials to complete the review of the treatment indication.

US FDA has requested a new clinical programme to support approval of Prolia for the prevention of postmenopausal osteoporosis indication.

US The FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary for Prolia and must include a medication guide, a communication plan, and a timetable for submission of assessments of the REMS. US FDA acknowledged receipt of Amgen’s previously submitted proposed REMS materials. The FDA has also requested all updated safety data related to Prolia.

Amgen is reviewing the Complete Response Letter and will work with the FDA to determine the appropriate next steps regarding these applications.

“We are confident that we can quickly respond to the FDA’s requests for the treatment of postmenopausal osteoporosis indication and plan to do so in the near term,” said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen.

Amgen expects to receive a separate response for its application fordenosumab (Prolia) in the treatment and prevention of bone loss due to hormone ablation in breast and prostate cancer patients.

Amgen also has submitted denosumab (Prolia) for approval in postmenopausal osteoporosis and bone loss in breast and prostate cancer patients due to hormone ablation therapy in the European Union, Switzerland, Australia and Canada.

Nearly eight million women suffer from osteoporosis. The World Health Organization (WHO) has recently identified osteoporosis as a priority health issue along with other major non-communicable diseases,in the US today.

The economic burden of osteoporosis is comparable to that of other major chronic diseases; for example, in the U.S., the costs associated with osteoporosis-related fractures are equivalent to those of cardiovascular disease and asthma. It has been reported that osteoporosis results in more hospital bed-days than stroke, myocardial infarction or breast cancer.

Amgen’s BLA for  for Prolia for the treatment and prevention of osteoporosis in postmenopausal women and treatment and prevention of bone loss in women and men receiving hormone therapy for either breast cancer or prostate cancer was accepted in February 2009.

US FDA has provisionally approved the trade name Prolia in these proposed indications, for which the drug is administered twice yearly subcutaneously at a 60mg dose. The trade name is only for these indications and may not apply for other indications of denosumab.

Denosumab (Prolia) is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, an essential regulator of osteoclasts (the cells that break down bone).

Denosumab (Prolia) is being investigated for its potential to inhibit all stages of osteoclast activity through a targeted mechanism. It is being studied in a range of other bone loss conditions including rheumatoid arthritis, and cancer treatment-induced bone loss (in breast cancer and prostate cancer patients), as well as for its potential to delay bone metastases and inhibit and treat bone destruction across many stages of cancer.

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