The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a supplemental New Drug Application (sNDA) to the United States Food and Drug Administration (FDA) seeking full approval of BALVERSA® (erdafitinib), a kinase inhibitor, for the treatment of adults with locally advanced or metastatic urothelial carcinoma (mUC), that has susceptible fibroblast growth factor receptor (FGFR)3 genetic alterations and progressed during or after at least one line of a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor in the locally advanced or metastatic setting, or within 12 months of neoadjuvant or adjuvant therapy.
BALVERSA® was granted Breakthrough Therapy Designation by the US Food and Drug Administration in 2018 and accelerated approval in 2019 for the treatment of adults with locally advanced or metastatic UC with susceptible FGFR3 or FGFR2 genetic alterations who progressed during or after at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
Basis of sNDA submission of BALVERSA® (erdafitinib):
The sNDA submission for BALVERSA® is designed to meet regulatory requirements for confirming the clinical benefit of BALVERSA® based on randomised data from Cohort 1 of the Phase III THOR trial. The study’s primary endpoint of overall survival (OS) was fulfilled, with patients who took BALVERSA® obtaining a median OS of more than one year at the predetermined interim analysis data cutoff.
As the interim results met the predefined criteria for superiority of BALVERSA® treatment over chemotherapy, the independent data safety monitoring committee recommended that the study be halted and that patients randomised to chemotherapy be given the option to switch to BALVERSA®.
The observed BALVERSA® safety profile in THOR was similar with the known BALVERSA® safety profile in mUC. At the 2023 American Society of Clinical Oncology Annual Meeting, results from Cohort 1 were presented in a Late-Breaking Presentation Session (Abstract # LBA4619).
“BALVERSA continues to generate promising clinical findings for patients with FGFR-altered metastatic urothelial cancer, who often face poor disease outcomes,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “Through the ongoing development of this targeted therapy, we are committed to transforming bladder cancer treatment to positively impact the lives of patients.”
Brief History of BALVERSA:
Janssen Pharmaceutica NV and Astex Pharmaceuticals signed an exclusive worldwide licence and collaboration agreement in 2008 to develop and commercialise BALVERSA®.
BALVERSA® (erdafitinib) is a once-daily, oral FGFR kinase inhibitor approved by the United States Food and Drug Administration for the treatment of adults with locally advanced or metastatic UC who have susceptible FGFR3 or FGFR2 genetic alterations and have progressed during or after at least one line of platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
About THOR trial used in the sNDA filing of BALVERSA® (erdafitinib):
THOR (NCT03390504) is a multicenter, Phase 3 randomised, open-label trial examining the efficacy and safety of BALVERSA®. All of the patients in the research had metastatic or unresectable UC, had specific FGFR genetic mutations, and experienced disease progression during or after one or two prior lines of treatment.
The study compared Balversa in two cohorts:
Cohort 1:
The trial compared BALVERSA® to standard of care chemotherapy (investigators’ choice of docetaxel or vinflunine) after at least one line of treatment involving an anti-programmed death (ligand) 1 (PD-[L]1) drug.
Cohort 2:
BALVERSA® against pembrolizumab following one prior therapy that did not include an anti-PD-(L)1 agent.
After the clinical cutoff date, a long-term extension period is planned for the final analysis of each cohort for patients who continue to benefit from the study intervention.
The primary endpoint of the trial is OS; secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), patient-reported outcomes, safety, and pharmacokinetics (PK). Results from Cohort 1 were presented earlier this year at the 2023 ASCO Annual Meeting; data from Cohort 2 will be presented at a future medical meeting.
Other Clinical trials of Belversa:
In addition to the Phase 3 THOR study, BALVERSA® is being investigated in the Phase 2 THOR-2/BLC2003 study (NCT04172675), which compares BALVERSA® to investigator-choice intravesical chemotherapy in participants who previously received Bacillus Calmette-Guérin and relapsed with high risk non-muscle-invasive bladder cancer as well as the Phase 1 study (NCT05316155) of BALVERSA® in patients with non-muscle invasive or muscle invasive bladder cancer with select FGFR alterations, administered via the TARIS intravesical drug delivery system (TAR-210), which is designed to release BALVERSA® in the bladder to treat localised bladder cancer while reducing systemic toxicities.
