The Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom has approved Johnson & Johnson's (J&J) Balversa (erdafitinib) as a monotherapy for the treatment of adults with unresectable or metastatic urothelial carcinoma (UC), the most common form of bladder cancer. This approval targets patients with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations who have previously been treated with at least one line of therapy containing a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. The decision marks a significant advancement in precision medicine for bladder cancer patients with limited treatment options.
Basis of Approval: The THOR Phase III Trial
The MHRA's authorization is grounded in the findings from Cohort 1 of the Phase III THOR study, a randomized, open-label trial conducted across multiple clinical centers. The study compared the efficacy and safety of erdafitinib (n=136) against chemotherapy (n=130) in patients with advanced or metastatic UC with select FGFR alterations who had progressed on or after one or two prior treatments, including at least one PD-1 or PD-L1 inhibitor. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).
Clinical Impact and Expert Commentary
Professor Alison Birtle, consultant oncologist at Lancashire Teaching Hospitals NHS Foundation Trust, emphasized the importance of this approval: "Patients living with this advanced stage of bladder cancer, and whose tumors harbor FGFR3 alterations, require access to innovative precision therapies that can target the specific characteristics of their disease. Today’s authorization of erdafitinib, a targeted therapy that has been shown to significantly improve overall and progression-free survival for patients with FGFR3 alterations, will come as welcome news to eligible patients."
Erdafitinib: A Targeted FGFR Kinase Inhibitor
Erdafitinib, administered orally once daily, functions as an FGFR kinase inhibitor. It selectively inhibits the activity of FGFR3 alterations in cancer cells, demonstrating improved overall survival compared to chemotherapy in the second-line setting. The Phase III THOR study was halted in June 2023 based on the recommendation of an independent data safety monitoring committee after an interim analysis of efficacy and safety data. Patients initially randomized to chemotherapy (docetaxel or vinflunine) were offered erdafitinib as crossover therapy. Data showed a median OS exceeding one year in patients receiving erdafitinib, a significant improvement compared to the chemotherapy arm (12.1 months vs. 7.8 months; hazard ratio, 0.64; 95% confidence interval, 0.44 to 0.93; P=0.005).
Efficacy Data
Treatment with erdafitinib also demonstrated an improvement in median PFS compared to chemotherapy (5.6 months versus 2.7 months) and a confirmed ORR of 35.3% (48 out of 136 patients) versus 8.5% (11 out of 130 patients).
Company Perspective
John Fleming, country medical director at Johnson & Johnson Innovative Medicine UK, stated, "We are delighted that the MHRA has recognized the value that erdafitinib could bring to eligible patients with metastatic urothelial cancer. We look forward to progressing with HTA submissions for erdafitinib in the coming months, with the view to enabling eligible patients to access erdafitinib through the NHS as soon as possible."
Bladder Cancer Statistics and FGFR3 Alterations
In the UK, approximately 10,500 individuals are diagnosed with bladder cancer annually. Roughly 20% of those diagnosed with advanced or metastatic bladder cancer have FGFR3 alterations, which can drive cancer cell growth.
