The United States Food and Drug Administration has accepted AstraZeneca’s supplemental Biologics License Application (sBLA) for Imfinzi (durvalumab), providing it Priority Review status for muscle-invasive bladder cancer (MIBC) treatment.
The FDA assigns Priority Review to drug applications that, if approved, promise substantial benefits over current available treatments, enhancing either safety or effectiveness, helping prevent severe conditions, or improving patient adherence. The decision from the FDA on this application is expected by the second quarter of 2025, as per the Prescription Drug User Fee Act timeline.
Around 25% of bladder cancer patients present with muscle-invasive bladder cancer, where the tumor penetrates the bladder’s muscle wall without spreading distantly. In this context of curative intent, about 117,000 patients receive today’s standard treatment, which usually involves neoadjuvant chemotherapy and radical cystectomy. Despite this, high recurrence rates and poor outcomes persist after cystectomy.
Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, emphasized the necessity of novel treatments for muscle-invasive bladder cancer, stating: “Options for patients in this setting are critical since nearly half face cancer recurrence or progression despite curative attempts, including bladder removal. The FDA’s Priority Review designation underscores the pressing need for alternatives like Imfinzi, which aims to reshape standard care as the pioneering perioperative immunotherapy regimen to thwart recurrence and boost survival.”
The sBLA submission is underpinned by findings from the NIAGARA phase III trial, unveiled at a Presidential Symposium during the 2024 European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine.
In the trial, patients received either a combination of Imfinzi and neoadjuvant chemotherapy followed by Imfinzi monotherapy post-cystectomy or just the chemotherapy before cystectomy. A planned interim examination indicated that perioperative Imfinzi was associated with a 32% decrease in the likelihood of disease progression, recurrence, failure to undergo surgery, or mortality compared to the chemotherapy and cystectomy alone (indicated by an event-free survival [EFS] hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.56-0.82; p<0.0001). The median EFS hadn’t been reached in the Imfinzi group, contrasting with 46.1 months in the comparator group. After two years, 67.8% of patients treated with the Imfinzi regimen were event-free, compared to 59.8% in the control group.
In terms of overall survival (OS), a crucial secondary measure, the Imfinzi regime reduced death risk by 25% against the chemotherapy and cystectomy method (OS HR of 0.75; 95% CI 0.59-0.93; p=0.0106). The median survival had not been determined for either group. After two years, 82.2% of patients in the Imfinzi group remained alive against 75.2% in the control.
Imfinzi tolerated well, with no new safety issues emerging in neoadjuvant and adjuvant contexts. The consistency of adding Imfinzi to neoadjuvant therapy with conventional agents didn’t impede chemotherapy completion or surgical procedures compared to chemotherapy alone.
Regulatory considerations are ongoing in the EU, Japan, and other nations based on NIAGARA results.
Globally, bladder cancer ranks as the ninth most common cancer, with over 614,000 new diagnoses annually. Urothelial carcinoma, arising in the urinary tract’s urothelial cells, represents the most prevalent bladder cancer type, with many patients, notably half undergoing bladder removal, facing recurrence — highlighting a dire need for postoperative recurrence-preventing treatments.