FDA Round-Up: Erdafitinib for mUC, Enzalutamide for nmCSPC

By Zachary Bessette - Last Updated: August 30, 2023

Multiple genitourinary oncology therapies are in the spotlight this week, with new US Food and Drug Administration (FDA) indications potentially on the horizon.

The Janssen Pharmaceutical Companies of Johnson & Johnson announced their submission of a supplemental New Drug Application (sNDA) seeking full approval of BALVERSA (erdafitinib) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) who have a susceptible fibroblast growth factor receptor (FGFR)3 genetic alteration and disease progression after receiving at least 1 PD-1/PD-L1 inhibitor in the locally advanced or metastatic setting or within 12 months of neoadjuvant or adjuvant therapy.

Erdafitinib previously received Breakthrough Therapy Designation from the FDA in 2018 and received Accelerated Approval in 2019 for the treatment of adults with locally advanced or mUC who have susceptible FGFR3 or FGFR2 genetic alterations and who have progressed during or following at least 1 line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

The sNDA submission for full approval of erdafitinib requires verification of the safety and clinical benefit of the kinase inhibitor in a confirmatory trial—the phase 3 THOR study, which randomized patients to receive erdafitinib (n=136) or investigator’s choice of chemotherapy (n=130). After a median follow-up of 15.9 months, the median overall survival was 12.1 months versus 7.8 months, respectively. Median progression-free survival was 5.6 months versus 2.7 months, respectively.

These interim results met the predefined criteria for superiority of treatment with erdafitinib over chemotherapy, so the study was stopped and patients in the chemotherapy cohort were able to cross over to the erdafitinib arm.

Additionally, Pfizer Inc. and Astellas Pharma Inc. announced the FDA has accepted a priority review for the sNDA for XTANDI (enzalutamide) for the treatment of patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC) who have high-risk biochemical recurrence (BCR). The sNDA is based on results of the phase 3 EMBARK trial, which evaluated the safety and clinical benefit of enzalutamide across 3 treatment arms in patients with nmCSPC with high-risk BCR: enzalutamide plus leuprolide (n=355), placebo plus leuprolide (n=358), and enzalutamide monotherapy (n=355).

EMBARK met its primary end point of metastasis-free survival for the enzalutamide-plus-leuprolide arm, demonstrating a 58% reduction in the risk of metastasis or death over the placebo-plus-leuprolide arm.

To date, enzalutamide—in combination with leuprolide or as a monotherapy—has not been approved by any regulatory agency for the treatment of patients with nmCSPC and high-risk BCR.