FDA issued Amgen with a complete response letter stating it can’t approve the firm’s sBLA for use of Xgeva® (denosumab) as a treatment for men with castration-resistant prostate cancer (CRPC) who are at high risk of developing bone metastases. The agency said the submitted data didn’t show that the drug’s effect on bone metastases-free survival (BMFS) was great enough to outweigh the risks (including osteonecrosis of the jaw) in the intended population.
Consequently FDA has requested a trial or trials to demonstrate a favorable risk-benefit profile for Xgeva that can be generalized to the U.S. population. Amgen said it will review the CRL and work with FDA to decide on the next steps. The firm stresses that that the agency’s ruling has no effect on the already approved indication of Xgeva in the prevention of skeletal-related events (SREs) in men with prostate cancer-related bone metastases.
Xgeva is a fully human mAb Rank ligand inhibitor that is approved in the U.S., Canada, EU, and other territories for the treatment of SREs in patients with bone metastases from solid tumors but not multiple myeloma. In Japan, where Amgen is working with Daiichi Sankyo, denosumab is approved as Ranmark® for treating bone metastases from solid tumors and also bone complications resulting from multiple myeloma. Denosumab is also approved under the Prolia® trademark for treating postmenopausal osteoporosis and bone loss induced by hormone ablation therapy in breast or prostate cancer.
The drug achieved U.S. sales of $351 million in 2011. Amgen reported global Xgeva sales of in $409 million in 2011, and global Prolia sales of $203 million.
Marketing applications for Xgeva have been submitted in a number of other territories by Amgen and also by GlaxoSmithKline, which is collaborating with Amgen to commercialize Xgeva in countries where the latter doesn’t have a commercial presence. Xgeva is separately undergoing Phase III development for delaying or preventing bone metastases in breast cancer and prostate cancer as well as Phase II development for the treatment of giant cell tumor of the bone and RA.