BOSTON–enGene Therapeutics Inc. (Nasdaq: ENGN), a clinical-stage genetic medicines company with operations in Boston and Montreal, reported updated results from its Phase 2 LEGEND trial of detalimogene voraplasmid, an investigational gene therapy for bladder cancer, and announced plans to begin submitting a Biologics License Application (BLA) to the U.S. Food and Drug Administration by the end of 2026.
The updated findings from the trial’s pivotal Cohort 1 showed improvements across several measures of treatment effectiveness compared with an April 2026 analysis, including complete response rates and the duration of response.
Detalimogene is being developed for patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without accompanying papillary disease.
The trial enrolled 125 patients in Cohort 1, with 120 included in the efficacy analysis as of the October 29, 2026, data cutoff.
The complete response rate at any time increased to 56%, compared with 54% in the previous analysis. The preliminary Kaplan-Meier estimate of patients maintaining a response for at least 12 months rose to 43% from 25%.
Median duration of complete response also improved to 10.1 months from 8.6 months, while the 12-month landmark complete response rate increased to 24% from 13%.
“For patients with high-risk BCG-unresponsive NMIBC, we need therapies that provide meaningful and durable disease control while minimizing treatment-related toxicity and burden,” said Ashish M. Kamat, M.D., Professor of Urologic Oncology at The University of Texas MD Anderson Cancer Center and Primary Investigator of the LEGEND trial. “The updated LEGEND data are encouraging, demonstrating clinically meaningful antitumor activity with a favorable tolerability profile. Combined with its straightforward administration and handling requirements, detalimogene has the potential to become a valuable addition to our bladder-preserving treatment options, particularly in community urology practices where ease of administration and practical considerations can influence treatment selection.”
The latest analysis showed that median follow-up among responding patients increased to 12 months from 9.2 months in April, providing additional information about the durability of treatment responses.
According to enGene, all patients who entered maintenance treatment and had undergone durability assessments maintained their responses. Nine patients were still awaiting assessments needed to determine whether their responses had lasted at least 12 months.
The company also reported that 97% of efficacy-evaluable patients had not progressed to muscle-invasive or metastatic bladder cancer, while all responding patients remained free from progression to muscle-invasive disease in the bladder.
Additionally, 86% of all efficacy-evaluable patients and 96% of responders remained free from cystectomy, a surgical procedure to remove the bladder.
Safety findings were based on all 125 patients enrolled in Cohort 1. Treatment-related adverse events were reported in 59% of patients, with most classified as mild or moderate.
The most frequently reported side effects included fatigue in 21% of patients, painful urination and frequent urination in 16% each, and bladder spasms and urinary urgency in 13% each. Urinary tract infections were reported in 10% of patients.
Grade 3 treatment-related adverse events occurred in 4% of patients, while 2% experienced serious treatment-related adverse events. No Grade 4 or Grade 5 treatment-related adverse events were reported.
Treatment-related side effects led to discontinuation in 1% of patients and treatment interruption in 4%.
“The updated results from Cohort 1 demonstrate encouraging improvements across all key efficacy measures as the data have matured, bringing detalimogene’s efficacy profile to date within range of approved products for this indication,” said Ron Cooper, President and Chief Executive Officer of enGene. “Importantly, our recent interactions with the FDA provide a clear path to initiate a BLA submission before year-end 2026, representing a significant step toward bringing detalimogene to patients, with potential approval in 2027.”
The company said a recent pre-BLA meeting with the FDA resulted in agreement on several components of its planned regulatory submission, including the population of patients to be included in the primary efficacy analysis.
enGene expects to initiate the BLA submission before the end of 2026 and complete the application during the first half of 2027. The company is targeting potential FDA approval in 2027, subject to regulatory review.
If approved, detalimogene would become the first nonviral plasmid gene therapy for this indication, according to the company.
Unlike viral gene therapies, detalimogene uses a nonviral delivery approach designed for administration in urology practices. enGene believes the treatment’s administration and handling requirements could make it suitable for use across a broad range of clinical settings.
The company estimates that more than 75% of patients with high-risk, BCG-unresponsive NMIBC receive treatment in community urology practices, making accessibility outside major academic medical centers an important consideration for commercialization.
“In parallel, we are preparing for commercialization, with a focus on positioning detalimogene for broad adoption across community urology practices, where more than 75% of high-risk, BCG-unresponsive NMIBC patients receive care,” Cooper said. “We believe detalimogene’s differentiated ease of use and handling could facilitate integration into existing treatment settings, helping expand access to a new bladder-preserving treatment option for patients.”
enGene also plans to provide an update in mid-2027 on a separate LEGEND trial cohort evaluating detalimogene in combination with a surfactant bladder rinse.
The updated clinical results and planned regulatory filing represent significant milestones for enGene as it seeks to advance detalimogene toward potential commercialization as a bladder-preserving treatment for patients with limited therapeutic options.
