Imfinzi Granted FDA Priority Review for Less-Frequent, Fixed-Dose Use

AstraZeneca's Imfinzi (durvalumab) has received acceptance for its supplemental Biologics License Application (sBLA) and has also been granted Priority Review in the US for a new four-week, fixed-dose regimen for treatment in the approved indications of non-small cell lung cancer (NSCLC) and bladder cancer.

If approved, Imfinzi could be administered intravenously every four weeks at a fixed dose of 1500mg in unresectable Stage III NSCLC after chemoradiation therapy and previously treated advanced bladder cancer, consistent with the approved dosing in extensive-stage small cell lung cancer (ES-SCLC).

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that offer significant advances over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the fourth quarter of 2020.

If approved, the new dosing will be available as an alternative to the approved weight-based dosing of 10mg/kg every two weeks. The sBLA was based on data from several Imfinzi clinical trials, including results from the Phase III CASPIAN trial in ES-SCLC which used the four-week, fixed-dose regimen during maintenance.

“The new less-frequent dosing option for non-small cell lung cancer and bladder cancer will simplify and improve treatment by enabling continuity of care while minimising the risk of exposure to infection in the healthcare setting. This takes on particular urgency during the current pandemic, as doctors care for patients at high risk of COVID-19 complications. We are working with health authorities in the US and other countries to bring the option of four-week, fixed dosing for Imfinzi to patients around the world as soon as we can,” Dave Fredrickson, Executive Vice President, Oncology Business Unit, said.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the Phase III PACIFIC trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and several other countries. Additionally, it is approved in the US and under review in Japan and other countries for ES-SCLC. Imfinzi was also recently recommended for marketing authorization in the EU for this indication.

Stage III (locally-advanced) NSCLC is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery. Stage III disease is different from Stage IV disease, when the cancer has spread (metastasized), as the majority of Stage III patients are currently treated with curative intent.

Stage III NSCLC represents approximately one-third of NSCLC incidence and in 2015 was estimated to affect nearly 200,000 patients in the following eight key countries: China, France, Germany, Italy, Japan, Spain, UK, and the US, with approximately 43,000 cases in the US alone. The majority of Stage III NSCLC patients are diagnosed with unresectable tumors. Prior to approval of Imfinzi in this setting, no new treatments beyond chemoradiation therapy had been available to patients for decades.

In 2018, approximately 550,000 people were diagnosed with bladder cancer around the world and 200,000 died from the disease. Locally advanced and metastatic bladder cancer remains an area of unmet medical need and typically only one in seven patients are alive five years after diagnosis. Urothelial cancer (UC) is the most common form of bladder cancer. UC is the 10th most common cancer worldwide and the 13th most common cause of cancer death. PD-L1 is widely expressed in tumor and immune cells in patients with bladder cancer and helps tumors evade detection from the immune system.

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

As part of a broad development program, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumors.