Regulatory Decision Summary for Xgeva

Severe hypercalcemia of malignancy (HCM) is a life-threatening event that occurs at the end of life in patients with metastatic malignancies. There are limited treatment options for patients with HCM refractory to bisphosphonates. The efficacy of Xgeva to reduce albumin-corrected serum calcium (CSC) is demonstrated in patients with HCM refractory to intravenous bisphosphonates. Regarding the advanced age and poor prognosis of the study population, the safety profile of Xgeva is acceptable and is consistent with that reported in other studies with cancer populations. Cardiovascular events are a potential risk in cancer patients receiving Xgeva. Pharmacovigilance actions for cardiovascular events are included in the Xgeva Risk Management Plan. Colitis is not an identified risk or listed as a potential risk in cancer patients receiving Xgeva therapy. However, with a single case reported in this study, direct causality with Xgeva therapy cannot be established. Post-market monitoring is required for both adverse events. Overall, with appropriate product labelling and post-market monitoring, the benefit/risk profile of Xgeva is favorable in patients with HCM refractory to bisphosphonates.

Based on the evaluation of the data submitted, and as labelled, the Biologics and Genetic Therapies Directorate (BGTD) considers that Xgeva Supplement to a New Drug Submission (SNDS), Control #176891 for the indication of "Treatment of hypercalcemia of malignancy that is refractory to intravenous bisphosphonate" complies with the Food and Drug Regulations. A Notice of Compliance (NOC) is recommended.