FDA Selects Detalimogene for Manufacturing Pilot Program in NMIBC

The FDA has selected detalimogene voraplasmid (detalimogene; EG-70)—a novel non-viral gene therapy used for the treatment of patients with high-risk, Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without concomitant papillary disease—to participate in the Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) program, according to a news release from the drug’s developer, enGene Holdings.¹

According to the release, the FDA created the CDRP program to facilitate the development of therapies with compressed manufacturing timelines that have exhibited clinical benefits in patients who have had earlier access to them. Promoting earlier and more structured engagement between the FDA and sponsors on CMC development strategies, this collaboration aims to facilitate a scaling of manufacturing capacity as clinical development is ongoing.

Additionally, detalimogene has exhibited promising preliminary efficacy in the phase 2 LEGEND trial (NCT04752722), with an analysis conducted on 62 patients and 37 patients at 3 and 6 months, respectively.² In a previous news release from the company, among 62 patients who have completed at least 1 post-baseline disease assessment, the complete response (CR) rate was 63% (95% CI, 51%-74%), with a 3-month rate of 56% (95% CI, 44%-68%) and a 6-month rate of 62% (95% CI, 46%-76%). Of note, 4 patients successfully converted to a CR after reinduction; all 5 patients who completed the 9-month assessment experienced a CR.

“Careful selection of an appropriate bladder-sparing therapy is of utmost importance in creating a long-term strategy to maintain a patient’s disease control and quality of life, while minimizing the logistical burden on patient and practice,” Suzanne Merrill, MD, senior physician, urologic oncologist and bladder cancer regional lead at Colorado Urology, said in the news release on the preliminary LEGEND trial data.² “I am pleased to see the positive trajectory of detalimogene’s efficacy and tolerability data. Combined with its ease of use, detalimogene would be an attractive option to both patient[s] and a busy urology practice.”

Additionally, among 125 patients enrolled in the pivotal cohort in the trial, 42% had experienced a treatment-related adverse effect (TRAE). Moreover, 1.6% had experienced TRAE-related dose reductions, and 0.8% discontinued treatment due to TRAEs.

The open-label phase 2 LEGEND trial enrolled patients with high-risk, BCG-unresponsive NMIBC with CIS with or without papillary disease in the pivotal cohort, with 3 additional cohorts featuring patients with NMIBC with CIS who are BCG naive, those with NMIBC with CIS who received insufficient BCG treatment, and those with BCG-unresponsive high-risk NMIBC with papillary-only disease.

Those in the phase 2 trial received up to four 12-week cycles of drug instillations.³ Complete responders following the 4 cycles received up to an additional 4 cycles of maintenance treatment, and if responses were maintained, up to another additional 4 cycles for a maximum of 12 cycles.

In the phase 1 portion of the trial, detalimogene was given via bladder instillation at 50 mL via catheter at a 2-dose regimen on days 1 and 8 or a 4-dose regimen on days 1, 8, 29, and 36. Maintenance treatment in the phase 2 portion of the trial was given as 2 doses per bladder instillation for each 12-week cycle.

The primary end point of the phase 1 portion of the trial was incidence and severity of AEs. In the phase 2 portion of the trial, it was the 48-week cystoscopic CR rate. Secondary end points included dose-limiting toxicities; progression-free survival; CR rate at 12, 24, 36, and 96 weeks; duration of response; and quality of life.

The FDA has previously granted detalimogene regenerative medicine advanced therapy (RMAT) and fast track designations as a treatment for patients with high-risk, BCG-unresponsive NMIBC with CIS with or without papillary disease. Additionally, the developers plan to submit a biologics license application in the second half of 2026.

“Manufacturing readiness in drug development is often underappreciated. We have already scaled detalimogene manufacturing to commercial-level, and CDRP is expected to help ensure CMC readiness for filing and commercialization,” Ron Cooper, president and chief executive officer of enGene Holdings, said in the news release on detalimogene’s selection for the CDRP program.¹ “Our progress on the manufacturing front is in sync with detalimogene clinical development, where we recently announced improved 6-month [CR] rate in the LEGEND trial pivotal cohort.”

References

1. enGene’s detalimogene selected for FDA Manufacturing Pilot Program to support manufacturing readiness. News release. enGene Holdings. December 2, 2025. Accessed December 3, 2025. https://tinyurl.com/4ykvzff7
2. Detalimogene demonstrates improved complete response rate of 62% at 6 months. News release. enGene Holdings. November 11, 2025. Accessed December 3, 2025. https://tinyurl.com/5f73nxda
3. LEGEND study: EG-70 in NMIBC patients BCG-unresponsive and high-risk NMIBC incompletely treated with BCG or BCG-naïve. ClinicalTrials.gov. Updated September 4, 2025. Accessed December 3, 2025. https://tinyurl.com/46hbnnca