enGene Snags FDA RMAT Designation for Bladder Cancer Gene Therapy Detalimogene

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to enGene'sdetalimogene voraplasmid (also known as detalimogene, and previously referred to as EG-70), an investigational nonviral immuno-oncology gene therapy, for the treatment of high-risk bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC) with carcinoma in situ.¹

“Detalimogene has the potential to deliver what NMIBC patients and their physicians have long needed—a nonviral option with optimized delivery to the bladder, safety in handling, and ease of administration,” Ron Cooper, BSc, the chief executive officer of enGene, told CGTLive® in response to a request for comment. “We’re pleased to receive this designation for detalimogene and are encouraged that we’re one step closer to potentially providing NMIBC patients a new option that may help transform the treatment landscape.”

Detalimogene is expected to be able to be utilized in urology clinics in a streamlined manner and is intended to provide an additional option for patients who might have few options besides radical cystectomy. The gene therapy is currently being evaluated in the phase 1/2 LEGEND clinical trial (NCT04752722). According to enGene, data from this study informed the FDA’s decision to grant RMAT designation to detalimogene.

“Receiving the RMAT designation highlights the promising profile of detalimogene and its potential to address the high unmet need in NMIBC,” Cooper added in a press release provided by enGene.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.”

Earlier in June, enGene noted in a business update that it continues to see “strong enrollment” in LEGEND and that it expects that it may potentially file a biologics license application for detalimogenewith the FDA in the middle of 2026.² The company also stated that is has shared preclinical and clinical data related to detalimogene with the European Medicines Agency (EMA) in the context of an EMA Scientific Advice process. Pending a positive benefit-risk ratio is seen, the EMA suggested that it “broadly agrees” the shared data could support a conditional marketing authorization application submission for detalimogene.

In June of last year, CGTLive covered the design of the LEGEND trial as part of our Clinical Trials in Progress series. The multicenter clinical trial consists of a now-completed dose-escalation portion (phase 1) focused on safety and an efficacy-focused portion (phase 2). The primary end point for the phase 1 portion of LEGEND consists of the nature, incidence, relatedness to treatment, and severity of all treatment-emergent adverse events (TEAEs) and serious TEAEs that occur during a 2-year timeframe. The phase 2 portion’s primary end points include the percentage of patients with a cystoscopic complete response (CR) at 48 weeks posttreatment, as assessed by the cystoscopy exam, urine cytology, bladder biopsies, and the nature, incidence, relatedness to treatment, and severity of TEAEs that occur during a 3-year timeframe.

“enGene’s phase 1/2 LEGEND study is designed to demonstrate the potential of EG-70 across a broad group of high-risk NMIBC patients, encompassing patients who are unresponsive to BCG as well as those who are naïve to BCG or were unable to receive a full course of treatment due to the ongoing global BCG shortage," Jason Hanson, JD, at the time the CEOof enGene, said in a statement issued to CGTLive in June 2024. "In light of our recently announced decision to expand the study with a third cohort of patients who are BCG-unresponsive with high-risk papillary-only NMIBC, we believe LEGEND is well-positioned to generate a comprehensive dataset in support of EG-70’s use across a spectrum of high-risk NMIBC patients. Furthermore, EG-70 is a nonviral gene therapy candidate designed for straightforward intravesical administration at the point of care and to be well-suited for use in community- and high-volume urology clinics where the majority of NMIBC patients are treated. EG-70 has no thaw process, BSL2-like handling requirements, or pre- or post-treatment requirements for patients.”

REFERENCES
1. FDA grants RMAT designation for enGene’sdetalimogene, enabling potential for expedited review in high-risk, non-muscle invasive bladder cancer. News release. enGene Holdings Inc. June 25, 2025. Accessed June 25, 2025. https://engene.com/fda-grants-rmat-designation-for-engenes-detalimogene-enabling-potential-for-expedited-review-in-high-risk-non-muscle-invasive-bladder-cancer/
2. enGene reports second quarter 2025 financial results and provides business update. News release. enGene Holdings Inc. June 12, 2025. Accessed June 25, 2025. https://engene.com/engene-reports-second-quarter-2025-financial-results-and-provides-business-update/