FDA Accepts Biologics License Application for Durvalumab in Bladder Cancer

Approval decision expected early next year

The FDA has accepted the first biologics license application (BLA) for durvalumab (AstraZeneca/MedImmune), a programmed death ligand-1 (PD-L1) human monoclonal antibody (mAb), and has granted the medication priority review status, with a Prescription Drug User Fee Act (PDUFA) action date set for the second quarter of 2017.

The BLA submission for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) whose disease has progressed during or after one standard platinum‑based regimen follows a breakthrough therapy designation for durvalumab, granted in February 2016.

Durvalumab is being tested as monotherapy and in combination with tremelimumab (CTLA-4 mAb) in the phase 3 DANUBE trial as first-line treatment for patients with metastatic UC, regardless of eligibility for cisplatin-based chemotherapy.

The combination of durvalumab and tremelimumab is also being studied in phase 3 trials in non–small-cell lung cancer and head-and-neck squamous-cell carcinoma, and in phase 2 and earlier trials in gastric cancer, pancreatic cancer, hepatocellular carcinoma, and blood cancers.

Durvalumab is an investigational human mAb directed against PD-L1. PD-L1 is expressed by tumors to evade detection by the immune system through binding to programmed death-1 (PD-1) proteins on cytotoxic T lymphocytes. Durvalumab blocks the PD-L1 interaction with PD-1, thereby countering the tumor’s immune-evading tactics. 

Urothelial bladder cancers arise from the epithelium of the bladder and are the ninth most common form of cancer worldwide. The Global Burden of Disease Cancer Collaboration has estimated that there were 400,000 incidents of bladder cancer and 173,000 deaths worldwide in 2013. Metastatic bladder cancer has a five-year overall survival rate of less than 15%.

Sources: AstraZeneca; December 9, 2016; and AstraZeneca; February 17, 2016.