enGene Reports Updated LEGEND Phase 2 Data Showing 62% Complete Response Rate at Six Months for Detalimogene Voraplasmid in BCG-Unresponsive NMIBC
enGene Holdings Inc. (Nasdaq: ENGN) (“enGene” or the “Company”), a clinical-stage, non-viral genetic medicines company, today announced updated preliminary data from the pivotal cohort of its ongoing Phase 2 LEGEND trial evaluating detalimogene voraplasmid (also known as detalimogene and previously EG-70) for the treatment of high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) patients with carcinoma in situ (CIS), with or without concomitant papillary disease.
The new data, presented from patients treated under the amended LEGEND protocol, highlight continued improvements in efficacy and reinforce the Company’s plan to submit a Biologics License Application (BLA) for detalimogene in the second half of 2026.
Encouraging Preliminary Results from the Pivotal Cohort
The latest analysis included 62 patients evaluated at three months and 37 patients at six months, all treated under the updated LEGEND trial protocol. The amendment, implemented in the fourth quarter of 2024, was designed to better align the study with the American Urological Association (AUA) guidelines and current standards of care for NMIBC.
Key efficacy results from the 62-patient cohort enrolled under the amended protocol include:
- 63% Complete Response (CR) rate at any time (n=62)
- 56% CR rate at three months (n=62)
- 62% CR rate at six months (n=37), including four patients who converted to CR following reinduction
- 100% CR at nine months among the five patients who had reached this timepoint
These findings demonstrate a clear improvement in treatment response and durability compared to earlier data reported prior to the protocol update.
Favorable Tolerability Profile and Treatment Experience
The pivotal cohort, which ultimately enrolled 125 patients—surpassing the initial target by 25%—also continues to demonstrate a strong tolerability and safety profile.
Key safety observations include:
- 42% of patients experienced treatment-related adverse events (TRAEs)
- Only 1.6% of patients experienced dose interruptions due to TRAEs
- Merely 0.8% of patients had dose discontinuations as a result of TRAEs
Most TRAEs were Grade 1 or 2, transient, and manageable in a routine outpatient setting.
“We are pleased to report an improved six-month CR rate for patients treated under the amended LEGEND protocol,” said Hussein Sweiti, M.D., MSc, Chief Medical Officer at enGene. “With a competitive efficacy profile and the potential for best-in-class tolerability and ease of use, we believe detalimogene could emerge as a leading first-line therapy for patients with high-risk, BCG-unresponsive NMIBC.”
“Selecting the right bladder-sparing therapy is essential to preserve long-term disease control and patient quality of life,” added Suzanne Merrill, M.D., Senior Physician, Urologic Oncologist, and Bladder Cancer Regional Lead at Colorado Urology. “Detalimogene’s emerging data profile—combining efficacy, tolerability, and convenience—positions it as a particularly appealing option for both patients and urology practices.”
Comparison of Pre- and Post-Protocol Amendment Populations
Earlier in September 2024, enGene reported preliminary data from 21 patients enrolled before the protocol amendment and an additional 10 patients enrolled afterward under the same version, totaling 31 patients treated under the previous protocol.
The following summarizes efficacy outcomes across both patient subgroups:
| Population | Any Time CR (%) | 3-Month CR (%) | 6-Month CR (%) |
|---|---|---|---|
| Post-Protocol Amendment (n=62) | 63% (CI: 51–74) | 56% (CI: 44–68) | 62% (CI: 46–76) |
| Pre-Protocol Amendment (n=31) | 55% (CI: 38–71) | 55% (CI: 38–71) | 41% (CI: 25–59) |
Data as of October 24, 2025. The intent-to-treat (ITT) population includes all patients who received at least one dose of treatment and had at least one post-baseline disease assessment. Six-month CR rates include only patients evaluable at that timepoint or those with earlier progression.
These results illustrate a notable improvement in response rates following the protocol amendment. Earlier data collected under the prior design showed a markedly lower 12-month CR rate, falling short of results seen with currently FDA-approved products for BCG-unresponsive NMIBC. The enhanced outcomes observed with the updated study design underscore the potential clinical benefit of detalimogene and support its continued advancement toward regulatory submission.
Regulatory Alignment and Trial Design Updates
Following constructive discussions with the U.S. Food and Drug Administration (FDA), enGene has confirmed updates to the primary and secondary endpoints of the LEGEND study’s pivotal cohort:
- The primary endpoint has been revised from 12-month landmark CR rate to CR rate at any time, a metric more reflective of clinical response and consistent with other FDA-registered NMIBC programs.
- The key secondary endpoint will now be duration of response (DOR) among patients achieving CR.
In addition, enGene plans to finalize a statistical analysis plan (SAP) with the FDA to define the final efficacy evaluable population for its pivotal data set.
Progress Across LEGEND Trial Cohorts
Beyond the pivotal cohort, enGene continues to make steady progress across multiple parallel cohorts within the LEGEND trial:
- Cohort 2a: Evaluating detalimogene in NMIBC patients with CIS who are naïve to BCG therapy – 30 patients enrolled
- Cohort 2b: Evaluating detalimogene in high-risk NMIBC patients with CIS who have been exposed to BCG but not adequately treated – 45 patients enrolled
- Cohort 3: Evaluating detalimogene in BCG-unresponsive, high-risk NMIBC patients with papillary-only disease – 36 patients enrolled
These additional patient groups will further inform the therapeutic potential of detalimogene across diverse NMIBC subtypes and treatment histories.
“We are highly encouraged by the consistent and strengthening data emerging from the LEGEND trial,” said Ron Cooper, President and Chief Executive Officer of enGene. “Detalimogene’s clinical profile, combined with its straightforward administration and non-viral platform, underscores its potential to transform the NMIBC treatment landscape. We continue to view detalimogene as a significant commercial and medical opportunity.”
Upcoming Clinical and Regulatory Milestones
enGene has outlined a series of key upcoming milestones as the LEGEND program advances toward regulatory submission and potential approval:
- The Company plans to provide an updated data release from the pivotal LEGEND cohort in the second half of 2026, following alignment with the FDA on the SAP and once a sufficient number of 12-month CR data points have been collected.
- enGene expects to file a BLA with the FDA in H2 2026, supported by the full pivotal dataset and additional durability analyses.
- Subject to regulatory review, the Company anticipates a potential FDA approval in 2027.
These milestones position detalimogene as one of the most advanced, non-viral genetic therapies in late-stage development for NMIBC.
Detailed Safety Profile
Detalimogene continues to exhibit an excellent safety and tolerability profile across all evaluated patients. As of October 24, 2025, safety data from 125 patients in Cohort 1 showed that 53 patients (42%) experienced at least one TRAE. The majority were mild to moderate (Grade 1/2) and transient in nature. Only three patients experienced Grade 3 TRAEs, and no Grade 4 or Grade 5 TRAEs were reported.
The most frequently observed TRAEs were:
- Fatigue – 16.8%
- Dysuria (painful urination) – 12.0%
- Bladder spasm – 10.4%
- Micturition urgency – 10.4%
- Pollakiuria (frequent urination) – 10.4%
Importantly, there were no treatment-related discontinuations due to severe adverse events. This favorable tolerability, coupled with the product’s non-viral delivery system, reinforces detalimogene’s potential as a well-tolerated, outpatient-administered intravesical therapy for NMIBC.
About the LEGEND Trial
The Phase 2 LEGEND trial is an open-label, multicenter study evaluating the efficacy and safety of detalimogene voraplasmid, a non-viral plasmid DNA-based therapy engineered to activate innate and adaptive immune responses within the bladder tumor microenvironment. The trial is being conducted in multiple cohorts, targeting different NMIBC populations ranging from BCG-naïve to BCG-unresponsive patients.
The pivotal cohort (Cohort 1) specifically targets patients with carcinoma in situ (CIS), with or without concomitant papillary disease, who have failed BCG therapy. The trial’s endpoints—complete response rate and duration of response—are designed to support registration with the FDA.
Conference Call and Webcast Information
enGene will host a conference call and live webcast today, November 11, 2025, at 8:00 a.m. ET, to discuss the updated LEGEND trial data and provide additional corporate updates.
Participants can access the live webcast via enGene’s Investor Relations website on the Events and Presentations page. The webcast will be accompanied by an investor presentation slide deck.
Interested participants may register for the live call through the registration link available on the same page. Following registration, they will receive dial-in details for the event. A replay of the webcast will remain available on the Company’s website for one year.
About enGene Holdings Inc.
enGene Holdings Inc. (Nasdaq: ENGN) is a clinical-stage genetic medicines company developing non-viral, intravesical therapies designed to locally deliver genetic material and activate immune responses for the treatment of serious diseases, beginning with bladder cancer.
The Company’s lead program, detalimogene voraplasmid, utilizes enGene’s proprietary non-viral delivery platform to stimulate immune activation directly within the bladder, without the safety concerns typically associated with viral vectors.
enGene’s mission is to harness non-viral genetic delivery technologies to create new treatment paradigms for diseases that are inadequately addressed by current therapeutic options. For more information, visit www.engene.com.
This press release contains forward-looking statements, including statements regarding the potential clinical and commercial success of detalimogene voraplasmid, the anticipated timing of data readouts, BLA submission, and potential FDA approval. Actual results may differ materially from those indicated due to a variety of risks and uncertainties, including clinical, regulatory, and operational factors. enGene undertakes no obligation to update forward-looking statements except as required by law.
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