Xgeva for mets Credit: Amgen

The US Food and Drug Administration approved Amgen's monoclonal antibody (mAb) Xgeva (denosumab), which targets the receptor activator of NF-κB ligand (RANKL) to reduce skeletal-related events in individuals with bone metastasis from solid tumors. The agency's go-ahead, announced in November, was based on three pivotal phase 3 trials comparing the human anti-RANKL mAb with the standard of care bisphosphonate Zometa (zoledronic acid) from Novartis of Basel. Results from the three Xgeva trials—one in people with castration-resistant prostate cancer, one in breast cancer and one in individuals with solid tumors or multiple myeloma—show Xgeva's superiority in breast and prostate cancer trials and noninferiority to Zometa in solid tumors and multiple myeloma. Xgeva also reduced pain and improved quality of life compared with Zometa. “Xgeva could eat into the existing market share of the bisphosphonates,” says Ranjith Gopinathan, industry analyst in life sciences at Frost & Sullivan. “Xgeva is expected to generate sales of about $2.4 billion in 2015,” Gopinathan adds. The Thousand Oaks, California–based company's mAb was already approved back in June 2010 as Prolia to treat osteoporosis in postmenopausal women (Nat. Biotechnol. 28, 640, 2010). The dose given to cancer patients is 12 times higher than to patients with bone loss indications, but so far the antibody has not shown the worrying side-effects associated with bisphosphonates, which include renal toxicity, atypical fractures of the thigh and osteonecrosis of the jaw. As questions mount over bisphosphonate use, clinicians may well favor treatment with the biologic. Robert Coleman, professor of medical oncology at Sheffield University, UK, believes Xgeva could potentially replace bisphosphonates as standard of care because of its efficacy, ease of administration (Xgeva is injected subcutaneously and Zometa is an intravenous infusion) and less severe side effects. “The only limitation could be the cost—many of the bisphosphonates are just about to come off patent, so doctors would need to balance cost and efficacy,” says Coleman. Amgen is currently developing denosumab for rheumatoid arthritis, and rare giant cell tumors of the bone, which are very dependent on RANKL.