enGene NASDAQ: ENGN reported preliminary data from the pivotal Cohort 1 of its ongoing Phase 2 LEGEND trial evaluating detalimogene voroplasmide, or detalimogene, in patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ.
On a company call, President and Chief Executive Officer Ron Cooper said the latest readout showed that detalimogene’s complete response rate at any time, the study’s primary endpoint, and its Kaplan-Meier estimated 12-month complete response rate are “currently tracking within range of approved products.” However, he also said the durability data remain incomplete and that efficacy was “at the lower end” of the company’s expectations.
The company said it plans to provide longer-term durability data for all of Cohort 1 in the second half of the year and continue discussions with the U.S. Food and Drug Administration regarding its statistical analysis plan and a potential biologics license application filing.
Preliminary Cohort 1 Data
Chief Medical Officer Hussein Sweis said LEGEND’s pivotal Cohort 1 enrolled 125 patients, with 124 having completed the three-month assessment as of the April 21 data cutoff. The median age was 71, just over 80% of patients were male and the median number of prior BCG doses was 12. Sweis said the population included high-risk characteristics, including nearly 40% with carcinoma in situ plus papillary disease and 25% who had received prior therapy other than BCG.
Among 124 evaluable patients, the complete response rate at any time was 54%, while the complete response rate at six months was 43%. Sweis said that among the 52 patients who were responders at six months, 37 of 44 evaluable patients were in complete response at the nine-month assessment, with nine patients pending evaluation. At 12 months, 13 of 22 evaluable patients were in complete response, with 11 patients pending assessment.
The company also reported complete response rates at nine and 12 months of 33% and 13%, respectively, but said those datasets remain immature. Cooper later said the Kaplan-Meier estimated 12-month landmark complete response rate was 25%, with a 95% confidence interval of 11% to 41%, and median duration of response was 8.7 months.
Lower Response in Later-Assessed Patients
Cooper said that in a prior update, enGene had highlighted improvements in complete response rates among 62 of 94 patients enrolled following a protocol amendment implemented in the fourth quarter of 2024. At that time, 32 patients enrolled under the amended protocol had not yet reached their first disease assessment.
In the latest update, Sweis said those 32 patients had an anytime complete response rate of 39% and a six-month complete response rate of 32%, below previously reported rates in both pre-amendment and post-amendment groups. He said preliminary subgroup analysis did not identify discernible differences in demographics or disease characteristics that would explain the lower response rate.
“We are undertaking further analysis to see if we can determine a reason for the lower response rates seen in this population,” Sweis said.
The company also said the overall reinduction success rate was lower than expected and that fewer patients opted to undergo reinduction. Cooper said some non-responding patients elected to leave the study instead of being redosed under the protocol.
Safety Profile Remains a Focus
Sweis said detalimogene’s safety and tolerability profile remained consistent, with 55% of patients experiencing a treatment-related adverse event. Most events were mild, grade 1 or 2, localized and resolved quickly. The most frequent treatment-related adverse events were fatigue, dysuria, pollakiuria, micturition urgency and bladder spasm.
Six patients had grade 3 or greater treatment-related adverse events, all of which resolved. Treatment discontinuation due to treatment-related adverse events was 2.4%, and treatment interruption due to treatment-related adverse events was also 2.4%.
In response to an analyst question, Sweis said one grade 4 event involved elevated ALT, a liver enzyme. He said the investigator considered it potentially related to detalimogene, though the company did not necessarily agree with that assessment, and the event resolved without leading to discontinuation.
FDA Discussions and BLA Timing
During the question-and-answer session, Cooper said enGene believes the single-arm registration pathway in this indication remains intact, citing FDA draft guidance from 2018 and 2024 and prior product approvals using the pathway. He noted that the company has RMAT status and CDRP designation, which have supported ongoing engagement with the agency.
Cooper said enGene is in discussions with the FDA on its statistical analysis plan and expects further engagement after the Cohort 1 data are fully mature in the second half of the year. He said the FDA does not provide specific efficacy thresholds and would evaluate detalimogene based on its own dataset, including safety, efficacy and manufacturing.
The company said it has completed at-scale FDA validation manufacturing batches and expects detalimogene to have a low cost of goods among NMIBC immunotherapies, if approved.
Bladder Rinse Cohort and Commercial Research
Sweis said enGene has added a new LEGEND cohort incorporating a five-minute bladder rinse with polidocanol, an approved sclerosing agent, based on preclinical data showing a 10-fold increase in IL-12 expression over a two-week period, shorter dwell time and improved efficacy. The cohort is expected to enroll up to approximately 80 patients, with 20 trial sites activated and screening underway.
The surfactant rinse cohort will use the same dosing frequency but reduce total dwell time from 60 minutes to 30 minutes. Cooper said this work is independent of the planned BLA filing based on Cohort 1 and would be viewed as a lifecycle management opportunity.
Chief Global Commercialization Officer Amy Pott said enGene’s market research indicates that more than 80% of high-risk NMIBC patients are seen in community settings, where practices often have fewer resources and more constrained procedure room capacity. She said less than half of surveyed urologists across practice settings are prescribing novel branded therapies, citing difficult logistics and acquisition costs as key barriers.
Cooper said detalimogene’s potential advantages include a favorable tolerability profile, fewer administrations, regular freezer and refrigerator storage, and no need for special equipment or personnel. He said those attributes could make the therapy suitable for busy community urology practices if it is ultimately approved.
About enGene NASDAQ: ENGN
enGene Holdings Inc, through its subsidiary enGene, Inc, operates as a clinical-stage biotechnology company that develops genetic medicines through the delivery of therapeutics to mucosal tissues and other organs. Its lead product candidate is EG-70 (detalimogene voraplasmid), which is a non-viral immunotherapy to treat non-muscle invasive bladder cancer patients with carcinoma-in-situ (Cis), who are unresponsive to treatment with Bacillus Calmette-Guérin. The company was founded in 2023 and is based in Saint-Laurent, Canada.
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