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.
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.
PK (Selected data)
1. Tmax: 2.5 h.
2. Food Effect: No clinically meaningful differences.
3. Protein binding: 99.8%
4. Half-life: 59 h
5. Erdafitinib is primarily metabolized by CYP2C9 and CYP3A4.
6. Following a single oral dose of radiolabeled erdafitinib, approximately 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged).
API Properties and Ingredients
Erdafitinib is practically insoluble, or insoluble to freely soluble in organic solvents, and slightly soluble to practically insoluble, or insoluble in aqueous media over a wide range of pH values.
BALVERSA ®(erdafitinib) tablets are supplied as 3 mg, 4 mg or 5 mg film-coated tablets for oral administration and contains the following inactive ingredients:
Tablet Core: Croscarmellose sodium, Magnesium stearate (from vegetable source), Mannitol, Meglumine, and Microcrystalline Cellulose.
Film Coating: (Opadry amb II): Glycerol monocaprylocaprate Type I, Polyvinyl alcohol-partially hydrolyzed, Sodium lauryl sulfate, Talc, Titanium dioxide, Iron oxide yellow, Iron oxide red (for the orange and brown tablets only), Ferrosoferric oxide/iron oxide black (for the brown tablets only).
Orange Book Information (as of Jan 22, 2024)
For details and accuracy, please check with FDA website and its product insert.
Reference:
1. FDA website, Jan 22, 2024
2. Product Insert, Jan 22, 2024
