J&J’s Balversa Gains MHRA Marketing Authorization as Monotherapy for Bladder Cancer

On Nov. 6, 2024, Johnson & Johnson (J&J) announced that the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom has granted marketing authorization for Balversa (erdafitinib) to be used as a monotherapy in treating adults with unresectable or metastatic urothelial carcinoma (UC), which is the most common form of bladder cancer (1,2). This approved indication specifically covers eligible patients harboring susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations, and 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.

MHRA’s authorization is based on results from Cohort 1 of a Phase III study (THOR). The study was randomized, open-label, and spanned multiple clinical treatment centers. The study 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, where at least one of those treatments included a PD-1 or PD-L1 inhibitor. The study’s primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR), according to a company press release.

“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 National Health Service (NHS) Foundation Trust, in the press release. “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 administered orally as a once-daily, FGFR kinase inhibitor. It works by inhibiting the activity of FGFR3 alterations in cancer cells and has demonstrated an ability to extend overall survival compared to chemotherapy in the second-line setting (3).

In June 2023, the Phase III study (THOR) was stopped based on the recommendation of an independent data safety monitoring committee, following a review of efficacy and safety data of the study at interim analysis (3). All patients who were randomized to chemotherapy (docetaxel or vinflunine) were offered an opportunity to receive erdafitinib as crossover therapy, and results at the data cut-off timepoint showed that median OS of over one year was achieved in those patients receiving erdafitinib. These results marked a significant improvement compared to the patients in 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) (1).

Moreover, treatment with erdafitinib showed an improvement in median PFS compared to chemotherapy of 5.6 months versus 2.7 months and a confirmed ORR of 48 out of 136 patients (35.3%) versus 11 out of 130 patients (8.5%) (1).

“We are delighted that the MHRA has recognized the value that erdafitinib could bring to eligible patients with metastatic urothelial cancer,” said John Fleming, country medical director, Johnson & Johnson Innovative Medicine UK, in the release. “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 [health technology assessment] submissions for erdafitinib in the coming months, with the view to enabling eligible patients to access erdafitinib through the NHS as soon as possible.”

In the UK, approximately 10,500 people are diagnosed with bladder cancer each year, equating to 29 people every day (4). Of those diagnosed with advanced or metastatic bladder cancer, roughly 20% have FGFR3 alterations, which can drive the growth of cancer cells (5).

References

1. MHRA. Electronic Medicines Compendium, Balversa Summary of Product Characteristics. products.mhra.gov.uk (accessed November 6, 2024).
2. Leslie, S.W.; Soon-Sutton, T. L.; Aeddula, N. R. Bladder Cancer. In StatPearls; StatPearls Publishing, Aug. 15, 2024.
3. Loriot, Y.; Matsubara, N.; Park, S. H.; et al. Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. N. Engl. J. Med. 2023, 389 (21),1961–1971.
4. Cancer Research UK. Bladder Cancer Statistics. cancerresearchuk.org/health-professional/cancer-statistics/statistics-bycancer-type/bladder-cancer (accessed Nov. 6, 2024).
5. Xiao, J. F.; Caliri, A. W.; Duex, J. E.; Theodorescu, D. Targetable Pathways in Advanced Bladder Cancer: FGFR Signaling. Cancers (Basel). 2021, 13 (19), 4891.

Source: Johnson & Johnson