On January 19, 2024, the Food and Drug Administration approved erdafitinib (Balversa, Janssen Biotech) for adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible FGFR3 genetic alterations, as determined by an FDA-approved companion diagnostic test, whose disease has progressed on or after at least one line of prior systemic therapy. Erdafitinib 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 approval amends the indication previously granted under accelerated approval for patients with mUC with susceptible FGFR3 or FGFR2 alterations after prior platinum-containing chemotherapy.

Full prescribing information for Balversa will be posted here.

Efficacy was evaluated in Study BLC3001 Cohort 1, a randomized, open-label trial of 266 patients with mUC harboring selected FGFR3 alterations who had received 1-2 prior systemic treatments, including a PD-1 or PD-L1 inhibitor. Patients were randomized 1:1 to receive erdafitinib or investigator’s choice of chemotherapy (docetaxel or vinflunine). Randomization was stratified by region, performance status, and presence of visceral or bone metastases. FGFR3 alterations were identified from tumor tissue in a central laboratory by the therascreen FGFR RGQ RT-PCR kit (Qiagen) in 75% of patients, while the remainder were identified by local next generation sequencing assays.

The major efficacy outcome measure was overall survival (OS). Investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were additional outcome measures.

Statistically significant improvements in OS, PFS, and ORR were demonstrated for erdafitinib compared with chemotherapy. Median OS was 12.1 months (95% CI: 10.3, 16.4) for patients who received erdafitinib and 7.8 months (95% CI: 6.5, 11.1) for those who received chemotherapy (hazard ratio [HR] 0.64 [95% CI: 0.47, 0.88]; p-value=0.0050). Median PFS was 5.6 months (95% CI: 4.4, 5.7) for patients who received erdafitinib and 2.7 months (95% CI: 1.8, 3.7) for those who received chemotherapy (HR 0.58 [95% CI: 0.44, 0.78]; p-value=0.0002). Confirmed ORR was 35.3% (95% CI: 27.3, 43.9) for those who received erdafitinib and 8.5% (95% CI: 4.3, 14.6) for those who received chemotherapy (p-value<0.001).

The most common (>20%) adverse reactions, including laboratory abnormalities, were increased phosphate, nail disorders, diarrhea, stomatitis, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased aspartate aminotransferase, decreased sodium, increased creatinine, dry mouth, decreased phosphate, palmar-plantar erythrodysesthesia syndrome, dysgeusia, fatigue, dry skin, constipation, decreased appetite, increased calcium, alopecia, dry eye, increased potassium, and decreased weight.

The recommended erdafitinib dose is 8 mg orally once daily, with a dose increase to 9 mg once daily based on tolerability, including hyperphosphatemia, at 14 to 21 days. Treatment should continue until disease progression or unacceptable toxicity.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date

This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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