The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing authorisation for erdafitinib as a once-daily oral monotherapy for the treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC), harbouring susceptible FGFR3 genetic alterations who have previously received at least one line of therapy containing a PD-1 or PD-L1 inhibitor in the unresectable or metastatic treatment setting.

Erdafitinib is the first targeted therapy to receive a positive CHMP recommendation in this patient population. “FGFR alterations are important oncogenic drivers in urothelial carcinoma and can be associated with adverse clinical outcomes,” said Yohann Loriot, M.D., Ph.D., Institut Gustave Roussy and University of Paris-Saclay, France.

“As we aim to optimise treatment outcomes for patients, there is a significant unmet need for novel, targeted therapies that enable treatment decisions tailored according to a patient’s individual genetic and disease characteristics.” Europe has one of the highest rates of bladder cancer in the world, with nearly 225,000 patients diagnosed in 2022 representing a 10 percent increase from 2020.

The most common form of bladder cancer is UC, and up to 20 percent of patients with metastatic UC (mUC) have FGFR alterations. Unfortunately, prognoses remain poor for patients with mUC, with only eight percent of people diagnosed at a late metastatic stage surviving for five years or more.

“Today’s recommendation from the CHMP marks important progress towards transforming outcomes for patients diagnosed with bladder cancer with FGFR alterations. There is a critical need for a multidisciplinary care team approach, to identify patients who may benefit from erdafitinib through biomarker testing, ensuring the right treatment reaches the right patient at the right time,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “Pending approval, we look forward to providing eligible patients across the region with a new treatment option as soon as possible.”

The positive CHMP opinion is supported by data from Cohort 1 of the randomised, controlled, open-label multicentre Phase 3 THOR study (NCT03390504), evaluating the efficacy and safety of erdafitinib (n=136) versus chemotherapy (n=130) in patients with advanced or mUC with select FGFR alterations who have progressed on or after one or two prior treatments, at least one of which includes an anti-PD-(L) 1 agent.

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 (docetaxel or vinflunine) were offered the opportunity to cross over to erdafitinib. The results demonstrate median overall survival (OS) of over one year at the data cut-off, marking a significant increase as compared to those in the chemotherapy arm (12.1 months vs. 7.8 months; hazard ratio [HR], 0.64; 95 percent confidence interval [CI], 0.44 to 0.93; P=0.0050).

Treatment with erdafitinib also showed an improvement in median progression-free survival [PFS] compared to chemotherapy of 5.6 months versus 2.7 months (HR 0.58; 95 percent CI, 0.41 to 0.82; P=0.0002) and overall response rate [ORR] of 35.3 percent versus 8.5 percent.

Serious treatment-related adverse events (TRAEs) were observed in 13.3 percent of patients who received erdafitinib and 24.1 percent of patients randomised to chemotherapy. Grade 3 or higher adverse events were observed in 45.9 percent of patients on erdafitinib and 46.4 percent on chemotherapy.

Amongst patients who received erdafitinib, 8.1 percent had TRAEs that led to discontinuation of therapy, versus 13.4 percent of patients who received chemotherapy. TRAEs leading to death were reported in one patient who received erdafitinib and six patients who received chemotherapy.

“Erdafitinib has been shown to significantly improve outcomes for patients with FGFR3-altered urothelial carcinoma based on the THOR study results and represents an important new therapeutic option for these patients,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumours, Johnson & Johnson Innovative Medicine. “We are dedicated to advancing precision medicine approaches in oncology to improve patient outcomes, and this positive CHMP opinion is a significant milestone in our efforts to combat bladder cancer.”

Source: Johnson & Johnson