The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to detalimogene voraplasmid for the treatment of patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), enGene Holdings announced. The designation is intended to expedite the development and review process for regenerative medicines that demonstrate promising preliminary data.
"Receiving the RMAT designation highlights the promising profile of detalimogene and its potential to address the high unmet need in NMIBC," said Ron Cooper, CEO of enGene. "Bladder cancer patients with limited options cannot wait, and we are enthusiastic about potentially expediting the regulatory process to bring a first-in-class treatment to patients."
Promising Clinical Results Drive Regulatory Recognition
The RMAT designation was based on preliminary results from the ongoing pivotal LEGEND trial, which demonstrated compelling clinical activity in patients with BCG-unresponsive NMIBC with CIS. Preliminary data from cohort 1 in phase 2 of the study were presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.
At the time of data report, 26 patients were enrolled in cohort 1, consisting of 20 male patients and 6 female patients with a median age of 74 (range, 47 to 92). The overall complete response (CR) rate was 71% (15 of 21 evaluable patients). CR rates at 3- and 6-months were 67% (14 of 21) and 47% (8 of 17), respectively. The estimated 6-month CR rate per Kaplan-Meier was 51%.
Favorable Safety Profile Observed
The findings showed a promising safety and tolerability profile across the 42 patients who had received a dose of detalimogene in the trial. Overall, 20 patients (47.6%) reported a treatment-related adverse event (TRAE), all of which were grade 1/2. The most common TRAEs included dysuria (21.4%), bladder spasm (19.0%), pollakiuria (11.9%), and fatigue (11.9%).
Novel Non-Viral Gene Therapy Approach
Detalimogene is an investigational, non-viral gene-based immunotherapy designed to be instilled in the bladder to elicit an anti-tumor immune response. The therapy was developed using enGene's Dually Derivatized Oligochitosan (DDX) platform, a technology designed to overcome limitations of viral-based gene therapies and simplify manufacturing and administration processes.
The agent is designed for streamlined administration in urology clinics, including community practices where approximately 70% of urologists provide care. The FDA previously awarded detalimogene a Fast Track designation for BCG-unresponsive NMIBC with CIS with or without papillary tumors.
Comprehensive Clinical Development Program
Detalimogene is currently under evaluation in the pivotal phase 1/2 LEGEND trial, which is assessing the safety and efficacy of detalimogene across 4 patient cohorts. Cohort 1, which is intended to support the company's Biologics License Application for detalimogene, is assessing the agent in approximately 100 patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary disease.
The study is also enrolling patients with BCG-exposed NMIBC with CIS (cohort 2a), patients with NMIBC with CIS who have been exposed to BCG but have not received an adequate amount of treatment (cohort 2b), and patients with high-risk BCG-unresponsive NMIBC with papillary-only disease (cohort 3).
In the study, participants receive detalimogene at a dose concentration of 0.8 mg/mL in a 4-dose 50 mL instillation schedule at weeks 1, 2, 5, and 6 of a 12-week cycle. Following the 12-week cycle, patients with progressive disease may remain on detalimogene for up to 3 additional 12-week cycles.
Addressing Significant Unmet Medical Need
Non-muscle invasive bladder cancer occurs when cancer cells grow in the tissues that line the interior of the bladder, but the cancer has not yet penetrated the muscle of the bladder wall. About 75-80% of new bladder cancer diagnoses are NMIBC. Patients suffering from high-risk NMIBC who are unresponsive to the standard of care, Bacillus Calmette-Guérin (BCG), face high rates of disease recurrence (50-70%) and are subject to full removal of the bladder (cystectomy) as a curative but life-altering next step.
The RMAT designation provides enGene with several regulatory advantages, including early and frequent engagement with the FDA, potential for rolling review and priority review, and other benefits like Fast Track and Breakthrough Therapy designations.
Patients in the LEGEND study are being enrolled through clinical trial sites across the US, Canada, Europe, and the Asia-Pacific region. The primary end point is CR at 48 weeks, and secondary end points include safety and tolerability. Primary completion of the study is anticipated for June 2026.
