FDA grants RMAT designation to detalimogene voraplasmid for high-risk NMIBC

The FDA has granted a Regenerative Medicine Advanced Therapy (RMAT) designation to detalimogene voraplasmid (formerly EG-70) for the treatment of patients with high-risk BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), enGene announced in a news release.¹

Detalimogene is an investigational, non-viral gene-based immunotherapy.

The RMAT designation is intended to expedite the development and review process for regenerative medicines that demonstrate promising preliminary data. With this designation, the development process for detalimogene can benefit from intensive FDA guidance, as well as the potential for expedited review and opportunities for rolling or priority review.

“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, in the news release.¹ “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.”

Detalimogene is an investigational, non-viral gene-based immunotherapy designed to be instilled in the bladder to elicit an anti-tumor immune response. The FDA previously awarded detalimogene a Fast Track designation for BCG-unresponsive NMIBC with CIS with or without papillary tumors.

The agent is currently under evaluation in the pivotal phase 1/2 LEGEND trial (NCT04752722), 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).

Preliminary data from cohort 1 in phase 2 of the study were presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California.²

At the time of data report, 26 patients were enrolled in cohort 1, consisting of 20 male patients and 6 female patients. The median age of participants was 74 (range, 47 to 92).

The overall complete response (CR) rate was 71% (15 of 21). 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%.

The findings also showed a promising safety/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%).

Patients in the LEGEND study are being enrolled through clinical trial sites across the US, Canada, Europe, and the Asia-Pacific region. To be eligible for enrollment, patients need to be ineligible for or have elected not to undergo cystectomy and must have an ECOG Performance Score of 0 to 2 and satisfactory bladder function with the ability to retain the study drug for at least 60 minutes.

In the study, participants will 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.

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 2026.³

REFERENCES

1. FDA grants RMAT Designation for enGene’s detalimogene, enabling potential for expedited review in high-risk, non-muscle invasive bladder cancer. News release. enGene. Published online and accessed June 25, 2025. https://www.businesswire.com/news/home/20250625944717/en/FDA-Grants-RMAT-Designation-for-enGenes-Detalimogene-Enabling-Potential-for-Expedited-Review-in-High-Risk-Non-Muscle-Invasive-Bladder-Cancer

2. Taylor JA, Joshi S, Satkunasivam R, et al. Preliminary results from LEGEND: A phase 2 study of detalimogene voraplasmid (EG-70), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). J Clin Oncol. 2025;43(5). doi:10.1200/JCO.2025.43.5_suppl.802

3. LEGEND study: EG-70 in NMIBC patients BCG-unresponsive and high-risk NMIBC incompletely treated with BCG or BCG-naïve. ClinicalTrials.gov. Last updated June 11, 2025. Accessed June 25, 2025. https://clinicaltrials.gov/study/NCT04752722