FDA grants full approval for Balversa to treat locally advanced or metastatic bladder cancer with select genetic alterations

Johnson & Johnson announced today that the US Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for BALVERSA® (erdafitinib) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. BALVERSA® is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy. This FDA action converts the April 2019 accelerated approval of BALVERSA® to a full approval based on the clinical and overall survival benefit observed in the Phase 3 THOR study. BALVERSA® is the first oral FGFR kinase inhibitor to be approved, and the first and only targeted treatment for patients with mUC and FGFR alterations.

Approximately 20 percent of patients with mUC have FGFR3 genetic alterations. After one or more lines of systemic therapy, including a checkpoint inhibitor, these patients generally have a poor prognosis with few available treatment options. This approval is based on results from Cohort 1 of the randomised, controlled, open-label, multicentre Phase 3 THOR study (NCT03390504) confirming the clinical benefit of BALVERSA® in extending overall survival (OS) compared to chemotherapy in the second-line setting. Results from the study showed a 36 percent reduction in the risk of death with BALVERSA® versus chemotherapy in patients previously treated with a PD-1 or PD-(L)1 inhibitor, with those in the BALVERSA® arm living a median of over four months longer (Hazard Ratio (HR) 0.64; [95 percent Confidence Interval (CI), 0.47-0.88]; p=0.0050).¹

“Based on results from randomised Phase 3 data, BALVERSA continues to demonstrate the promise of targeted therapy in the treatment of patients with advanced bladder cancer,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. “This important milestone reinforces our commitment to advance innovative, precision therapies in oncology and confirm the role of targeted therapy in the treatment of bladder cancer.”

Warnings and precautions in the US prescribing information include ocular disorders, hyperphosphatemia and embryo-fetal toxicity. The most common (>20%) adverse reactions, including laboratory abnormalities, were increased phosphate, nail disorders, stomatitis, diarrhoea, increased creatinine, increased alkaline phosphate, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy.²

Johnson & Johnson is offering BALVERSA® and associated patient services through a single-source specialty pharmacy provider, US Bioservices. This model is part of the Company’s ongoing commitment to provide high-quality products, services, access, and support to healthcare professionals and patients.

The current full prescribing information is available at www.BALVERSA.com.

THOR (NCT03390504) is a Phase 3 randomised, open-label, multicentre study evaluating the efficacy and safety of BALVERSA®. All patients included in the study had metastatic or unresectable UC, with selected FGFR genetic alterations, and showed disease progression during or after one or two prior lines of treatment. The study compared BALVERSA® in two cohorts; BALVERSA® versus standard of care chemotherapy (investigator’s choice of docetaxel or vinflunine) after at least one line of treatment including an anti-programmed death (ligand) 1 (PD-[L]1) agent (Cohort 1); and BALVERSA® compared to pembrolizumab after one prior treatment not containing an anti-PD-(L)1 agent (Cohort 2). The trial consists of screening, a treatment phase (from randomisation until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment) and a post-treatment follow-up (from end-of-treatment to participant’s death, withdraws consent, or lost to follow-up study completion for the respective cohort, whichever comes first). A long-term extension period is planned for after the clinical cutoff date is achieved for the final analysis of each cohort for patients who continue to benefit from the study intervention. The primary endpoint of the study is OS; progression free survival (PFS), objective response rate (ORR), duration of response (DOR), patient-reported outcomes, safety, and pharmacokinetics (PK) are secondary endpoints.

Results from Cohort 1 were presented in a Late-Breaking Presentation Session (Abstract #LBA4619) at the 2023 American Society of Clinical Oncology Annual Meeting¹. In June 2023, based on the recommendation of the independent data safety monitoring committee, the THOR study was stopped at the interim analysis for efficacy and all patients randomised to chemotherapy were offered the opportunity to cross over to BALVERSA®. Results from Cohort 1 and Cohort 2 of the confirmatory, Phase 3, randomised study were presented at ESMO 2023 (Abstract #2359O), and results of Cohort 1 were published in the New England Journal of Medicine in November 2023.

BALVERSA® (erdafitinib) is a once-daily, oral FGFR kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations whose disease progressed on or after at least one line of prior systemic therapy. BALVERSA ® is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-(L)1 inhibitor therapy². Patients are selected for therapy based on an FDA-approved companion diagnostic for BALVERSA®. Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer is available at: http://www.fda.gov/CompanionDiagnostics.

BALVERSA® received Breakthrough Therapy Designation from the U.S. FDA in 2018 and received accelerated approval in 2019 for the treatment of adults with locally advanced or mUC which has susceptible FGFR3 or FGFR2 genetic alterations and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.³

The Company submitted a marketing authorisation application to the European Medicines Agency in September 2023 for BALVERSA ® as a treatment for adult patients with FGFR3-altered, locally advanced unresectable or metastatic urothelial carcinoma that has progressed following therapy with a PD-(L)1 inhibitor.

In 2008, Janssen Pharmaceuticals entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialise BALVERSA®.

For more information, visit www.BALVERSA.com.

Urothelial carcinoma, also known as transitional cell carcinoma, starts in the innermost lining of the bladder.⁴ It is the most common form of bladder cancer, representing more than 90 percent of all bladder cancers.⁵ Metastatic or unresectable disease is identified in approximately 20 percent of patients presenting with urothelial cancer, and an estimated five to eight percent of all bladder cancers. Approximately one in five patients (20 percent) diagnosed with mUC have an FGFR genetic alteration.^6,7 Fibroblast growth factor receptors are a family of receptor tyrosine kinases that can be activated by genetic alterations in a variety of tumor types, and these alterations may lead to increased tumor cell growth and survival. ^6,8,9,10,11 Select FGFR genetic alterations can be detected through an FDA-approved companion diagnostic. The five-year survival rate for patients with Stage IV metastatic bladder cancer that has spread to distant parts of the body is currently eight percent.¹²