Detalimogene voraplasmid shows promising activity in BCG-unresponsive NMIBC

Updated interim findings from the pivotal phase 2 LEGEND trial (NCT04752722) suggest that detalimogene voraplasmid may offer clinically meaningful activity with a manageable safety profile in patients with high-risk BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).^1,2

The results were presented at the 2026 American Urological Association Annual Meeting in Washington, DC, by Ashish M. Kamat, MD, MBBS.

“What we hear when [we] do patient advocacy events is that patients would like to see better durability and better response rates with the different treatments,” explained Kamat in an explanation of the unmet needs in the BCG-unresponsive space. “When we talk about different therapies, detalimogene voraplasmid is a non-viral gene therapy, and it's easy to administer and overcomes a few of the hurdles that we currently face.”

The updated analysis of LEGEND included 125 patients with BCG-unresponsive CIS with or without concomitant papillary disease who were either ineligible for or declined radical cystectomy.

Overall, the investigational intravesical gene therapy produced a complete response (CR) rate at any time of 54% (67 of 124 patients) and a 6-month CR rate of 43% (52 of 121 patients) among patients enrolled in the pivotal cohort of the study. The Kaplan-Meier estimate for 12-month duration of response was 25% (95% CI, 11% to 41%), and the reported rate of progression to muscle-invasive or more advanced disease was 3.2%.

About the LEGEND trial

LEGEND is evaluating detalimogene in patients with high-risk NMIBC. The pivotal cohort administered 4 intravesical doses during each 12-week cycle in the first treatment year, with reinduction permitted for persistent or recurrent disease. Patients achieving CR at 1 year transitioned to maintenance therapy. The primary end point was CR at any time, with secondary end points including duration of response, landmark CR rates, and safety.

Investigators reported that most responses occurred early, with 91% observed at the first disease assessment. Notably, at the time of data cutoff, 96.8% of patients were free from progression to T2 or greater disease, and 90.4% of patients had not required cystectomy.

Among responders at 6 months, 37 of 44 (84%) evaluable patients remained in CR at 9 months, while 13 of 22 (59%) evaluable patients maintained CR at 12 months. Investigators noted that additional patients (n = 21) remained pending evaluation, and some individuals (14%; 6 of 43) converted from nonresponse to CR following reinduction therapy.

Of the 32 patients whose first disease assessment occurred after the prior October 2025 data cutoff, efficacy outcomes were lower than previously observed, with CR rates of 39% at any time and 32% at 6 months. The company stated that preliminary subgroup analyses had not identified clear demographic or disease-related explanations and that further analyses were ongoing.

“These updated data continue to reinforce the favorable safety and tolerability profile of detalimogene and its clinical activity in a heavily pretreated, high-risk NMIBC patient population with limited therapeutic options,” said Ron Cooper, CEO of enGene, in the company’s news release.² ”Importantly, the low rate of progression to muscle-invasive disease leaves patients eligible for other bladder-sparing therapies.”

However, Cooper also acknowledged uncertainty regarding the durability findings, stating, “While durability outcomes to date are not what we hoped, these data are preliminary. We are focused on evaluating the totality of the data as it evolves and plan to continue to engage with the FDA and the medical community.”

The safety profile of the agent appeared generally manageable. Treatment-related adverse events (TRAEs) were reported in 55.2% of patients, with 91% of those events categorized as grade 1 or 2. Common TRAEs included fatigue, dysuria, urinary urgency, pollakiuria, and bladder spasm. Grade 3 TRAEs occurred in 4.8% of patients, and one grade 4 TRAE was reported and subsequently resolved. No grade 5 TRAEs occurred. Treatment discontinuations and interruptions due to TRAEs were each reported in 2.4% of patients.

Additional information on detalimogene

Detalimogene voraplasmid, previously known as EG-70, is an investigational, nonviral intravesical gene therapy designed to induce local innate and adaptive immune activation through the expression of 2 double-stranded RNAs and the cytokine interleukin-12. The agent was developed using enGene’s Dually Derivatized Oligochitosan platform, intended for local bladder delivery.

“The feedback from the urology community has been positive, and they have told us there is an important role for detalimogene,” added Katherine Chan, MD, MPH, executive director, urology clinical lead, enGene, in correspondence with Urology Times®. “While this is interim data, we are encouraged by the emerging efficacy, overall safety, and tolerability data, particularly given the high rate of CIS plus papillary disease patients and the number of heavily pretreated patients. Our durability data are interim, and we look forward to sharing more information as the data matures.”

Detalimogene previously received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA, which provides opportunities for expedited regulatory interactions for eligible regenerative medicine products. According to the company, manufacturing validation batches have been completed, and a statistical analysis plan has been submitted to the FDA as the program advances toward a potential biologics license application filing.

REFERENCES

1. Kamat AM, Tyson M, Rendon R, et al. A non-viral intravesical gene therapy for BCG-unresponsive NMIBC with CIS, with or without papillary disease: pivotal phase 2 interim results of detalimogene voraplasmid. Presented at: 2026 American Urological Association Annual Meeting; May 15-18, 2026; Washington DC. doi:10.1097/01.JU.0001192572.07890.f8.04

2. enGene announces updated interim results from LEGEND pivotal cohort. News release. enGene. May 7, 2026. Accessed May 16, 2026. https://engene.com/engene-announces-updated-interim-results-from-legend-pivotal-cohort/