Novel bladder cancer treatment gains MHRA approval in the UK

Johnson & Johnson has announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for BALVERSA^®▼ (erdafitinib) as a monotherapy for the treatment of adults with unresectable or metastatic urothelial carcinoma (UC), the most common form of bladder cancer. Specifically, the indication covers eligible patients harboring susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations, who have previously received at least one line of therapy containing a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor in the unresectable or metastatic treatment setting.

Approximately 10,500 people in the UK are diagnosed with bladder cancer every year, which equates to 29 people per day. Around 20 percent of people with advanced or metastatic bladder cancer have FGFR3 alterations, which can drive the growth of cancer cells.

“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,” said Professor Alison Birtle, Consultant Oncologist and Honorary Clinical Professor, Lancashire Teaching Hospitals NHS Foundation Trust. “Unfortunately, until now, there have been limited treatment options available for this group of patients, which may affect not only their prognosis, but their wellbeing and quality of life. 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, and highlights the importance of integrating biomarker testing into the treatment pathway for people with urothelial cancer, so that genetic alterations such as FGFR3 can be detected as early as possible.”

Erdafitinib is a once-daily, oral FGFR kinase inhibitor, which works by inhibiting the activity of FGFR3 alterations in cancer cells and has been shown to extend overall survival compared to chemotherapy in the second-line setting.

Today’s MHRA authorization is based on results from Cohort 1 of the Phase 3 THOR study, a randomized, open-label, multicenter study which evaluated the efficacy and safety of erdafitinib (n=136) versus chemotherapy (n=130) in patients with advanced or metastatic UC with select FGFR alterations who have progressed on or after one or two prior treatments, at least one of which includes a PD-1 or PD-L1 inhibitor. The primary endpoint of the study was overall survival (OS), with secondary endpoints being progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR).

In June 2023, based on the recommendation of the independent data safety monitoring committee, the THOR study was stopped following review of efficacy and safety data of the study at interim analysis. All patients randomized to chemotherapy (docetaxel or vinflunine) were offered the opportunity to receive erdafitinib as crossover therapy. The results show median OS of over one year was achieved in patients receiving erdafitinib at the data cut-off, marking a significant improvement compared to those in the chemotherapy arm (12.1 months vs. 7.8 months; hazard ratio [HR], 0.64; 95 percent confidence interval [CI], 0.44 to 0.93; P=0.005). Treatment with erdafitinib also showed an improvement in median PFS compared to chemotherapy of 5.6 months versus 2.7 months (HR 0.58; 95 percent CI, 0.41 to 0.82; P=0.0002) and a confirmed ORR of 48 out of 136 patients (35.3 percent) versus 11 out of 130 patients (8.5 percent).

The most common adverse reactions include hyperphosphatasemia (78.5 percent), diarrhea (55.5 percent), and stomatitis (52.8 percent). Adverse reactions leading to treatment discontinuation occurred in 19.4 percent of patients.

We are delighted that the MHRA has recognized the value that erdafitinib could bring to eligible patients with metastatic urothelial cancer. This milestone reflects J&J’s long-standing dedication to getting in front of cancer and delivering the most innovative precision therapies to patients in need. ​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.”

Dr. John Fleming, Country Medical Director, Johnson & Johnson Innovative Medicine UK