Detalimogene Shows 71% Complete Response in LEGEND Preliminary Analysis

enGene Holdings Inc., a clinical-stage genetic medicines company, has announced promising preliminary data from its ongoing pivotal cohort in the LEGEND study. The lead investigational product, detalimogene voraplasmid (detalimogene), is being evaluated in high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) patients with carcinoma in situ (Cis). The data revealed significant clinical activity and a favorable tolerability profile, aligning with earlier Phase 1 results.

The study assessed 21 patients at three months, with 17 of them also evaluated at six months. The Complete Response (CR) rates were impressive: 71% at any time, 67% at three months, and 47% at six months. Furthermore, detalimogene demonstrated a good safety profile, with no patients discontinuing treatment due to adverse events.

Dr. Raj Pruthi, Chief Medical Officer of enGene, expressed satisfaction with the preliminary results. He noted that the data enhances their confidence in detalimogene’s emerging profile and mentioned planned refinements in the LEGEND study protocol to further benefit patients. Suzanne Merrill, a urologist specializing in bladder cancer, highlighted the ease of handling and administration of detalimogene, emphasizing its potential as a widely used treatment option for NMIBC, particularly in community practice settings.

Bladder cancer remains a significant health issue in the United States, ranking among the top 10 cancers by incidence and incurring high annual treatment costs. NMIBC accounts for over 75% of bladder cancer diagnoses, and more than 70% of urologists treat these patients in community settings. Ron Cooper, CEO of enGene, pointed out that detalimogene was designed to be a practical therapy for urologists managing NMIBC. The early LEGEND study results underscore its potential to balance efficacy, tolerability, and ease of use effectively.

Safety data across all Phase 2 cohorts, including 42 patients, showed a favorable tolerability profile. Approximately 48% experienced at least one treatment-related adverse event (TRAE), primarily of Grade 1 or 2 severity. Notably, peripheral edema and urosepsis were the only Grade 3 TRAEs reported. Common TRAEs included dysuria, bladder spasm, pollakiuria, and fatigue, with no Grade 4 or 5 TRAEs observed.

The LEGEND study is a multi-cohort investigation aimed at establishing the efficacy of detalimogene in high-risk NMIBC patients with Cis and those with papillary-only NMIBC. The pivotal cohort involves around 100 patients in an open-label study who receive detalimogene intravesically at specified intervals over a 12-week cycle, up to four cycles, with periodic assessments. The primary efficacy endpoint is the percentage of complete responses at 12 months, evaluated through cystoscopy, urine cytology, and biopsy.

Additionally, enGene plans to start enrolling three more cohorts in the LEGEND study. These include high-risk BCG-exposed patients with Cis, BCG-naive patients with Cis, and high-risk BCG-unresponsive NMIBC patients with papillary-only disease. Enrollment for these cohorts is anticipated to begin in the fourth quarter of 2024, with the company aiming to file a Biologics License Application (BLA) for detalimogene in mid-2026.

enGene is a biotechnology company focused on delivering genetic medicines to treat diseases with high clinical needs. The company's lead program, detalimogene voraplasmid, addresses NMIBC and is being tested in the Phase 2 LEGEND study. The product leverages enGene’s proprietary Dually Derivatized Oligochitosan (DDX) platform, which facilitates the penetration of mucosal tissues and the delivery of various types of genetic material, including DNA and RNA.