Johnson & Johnson announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for BALVERSA®▼ (erdafitinib) as 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 who carry sensitive 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) inhibitor or a programmed death ligand 1 (PD-L1) inhibitor in unresectable or metastatic therapy.
Around 10,500 people in the UK are diagnosed with bladder cancer each year, which equates to 29 people a day. About 20 percent of people with advanced or metastatic bladder cancer have FGFR3 alterations, which can lead to the growth of cancer cells.
“Patients living with this advanced stage of bladder cancer and whose tumors host FGFR3 The changes require access to innovative precision treatments that can target the specific features 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 also their well-being and quality of life. Today’s approval of edafitinib, a targeted therapy shown to significantly improve overall progression-free survival for patients with FGFR3 alterations, will come as welcome news for eligible patients and highlights the importance of incorporating 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 that works by blocking the activity of FGFR3 alterations in cancer cells and has been shown to extend overall survival compared to second-line chemotherapy.
Today’s MHRA approval is based on results from Cohort 1 of the Phase 3 THOR study, a randomised, open-label, multicentre study that assessed the efficacy and safety of erdafitinib (n=136) versus chemotherapy (n=130) in patients with advanced or metastatic UC with selected FGFR alterations that have progressed on or after one or two prior therapies, 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 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 after review of the study’s efficacy and safety data at an interim analysis. All patients randomized to chemotherapy (docetaxel or vinflunine) were offered the opportunity to receive edafitinib as crossover treatment. The results show that a median OS of more than one year was achieved in patients receiving edafitinib at the data cut-off, with a significant improvement compared with 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). Edafitinib treatment also showed an improvement in median PFS compared with chemotherapy of 5.6 months versus 2.7 months (HR 0.58, 95 percent CI, 0.41 to 0.82, P=0.0002) and confirmed ORR of 48 out of 133 percent patients (35). 11 of 130 patients (8.5 percent);
The most common side effects include hyperphosphatasia (78.5%), diarrhea (55.5%) and stomatitis (52.8%). Adverse events leading to treatment discontinuation occurred in 19.4 percent of patients.
We are pleased that the MHRA has recognized the value that edafitinib could bring to eligible patients with metastatic urothelial cancer. This milestone reflects J&J’s long-standing commitment to tackling cancer and bringing the most innovative precision therapies to patients in need. We look forward to moving forward with HTA submissions for erdafitinib in the coming months, with a view to enabling suitable patients to access Erdafitinib through the NHS as soon as possible.”
Dr. John Fleming, Country Medical Director, Johnson & Johnson Innovative Medicine UK
