FDA starts speedy review of Imfinzi in bladder cancer

AstraZeneca could be just months away from FDA approval of a new bladder cancer indication for its PD-L1 inhibitor Imfinzi, which is viewed as key to meeting its sales ambitions for the drug.

The US regulatory agency has just started a priority review of Imfinzi (durvalumab), in combination with Pfizer and Astellas' nectin-4-targeting Padcev (enfortumab vedotin), as a perioperative regimen for patients with muscle-invasive bladder cancer (MIBC), and could deliver a decision before the end of the year.

The filing is based on the VOLGA trial in MIBC patients who are ineligible or refuse to take platinum-based chemotherapy, which showed that Imfinzi and Padcev given before surgery to remove the tumour, and Imfinzi on its own thereafter, significantly extended both event-free survival (EFS) and overall survival (OS) compared to standard therapy.

Bladder cancer is a key growth area for Imfinzi, which is already approved as a perioperative regimen for MIBC in combination with platinum chemo, based on the NIAGARA trial, and as an induction and maintenance therapy for non-muscle invasive bladder cancer (NMIBC) based on the POTOMAC study.

Sales of the drug are already strong, at more than $6 billion last year, and will be a key part of AZ's target of reaching $80 billion in total revenue by the end of the decade.

Around a quarter of bladder cancer cases fall under the MIBC category and, of these, up to half of patients are ineligible for cisplatin-based chemotherapy due to impaired renal function or other medical conditions and have generally had surgery to remove the bladder. Despite that radical treatment, they tend to be at an elevated risk of cancer recurrence.

AZ's head of oncology and haematology R&D, Susan Galbraith, said the FDA priority review "reinforces the potential of Imfinzi to become the immunotherapy backbone" for MIBC and, if approved, would be "the first perioperative regimen with enfortumab vedotin given only before surgery; a potentially new standard of care offering practice-changing efficacy and tolerability in this curative-intent setting."

Regulatory filings are currently under review in the EU, Japan, and several other countries based on the results of the VOLGA trial, said AZ.

The FDA review comes shortly after the agency approved MSD's subcutaneous PD-1 inhibitor Keytruda Qlex (pembrolizumab) with Padcev as a perioperative regimen for MIBC that can't be treated with the standard perioperative regimen of cisplatin plus gemcitabine. That regimen has also been approved in the EU.

Padcev is also approved in combination with Keytruda to treat previously untreated patients with locally advanced or metastatic urothelial carcinoma (UC), the most common form of bladder cancer, regardless of cisplatin eligibility.