EG110A is a novel gene therapy that uses a non-replicative herpes simplex virus-1 (HSV-1) vector allowing for the selective silencing of type C sensory neurons from the bladder to the dorsal root ganglia by expressing a transgene encoding the light chain of botulinum toxin F, under the control of the human calcitonin gene-related peptide promoter. In preclinical models of bladder overactivity, EG110A administration in the bladder wall resulted in retrograde transport of the HSV-1 vector to nuclei of C-type fibers located in the dorsal root ganglion, leading to transgene expression, inhibition of the reflex arc, and an increase in the bladder intercontraction interval. The objective of this first-in-human, ongoing clinical trial is to characterize the efficacy and safety of EG110A in adults with spinal cord injury (SCI) who suffer from neurogenic detrusor overactivity (NDO) and urinary incontinence (UI) treated by intermittent catheterization.

This open-label, phase 1b/2a dose-escalation trial is enrolling adults with SCI aged 18 to 75 years who experience NDO and UI. Participants receive 1 treatment course of EG110A, administered via 30 intradetrusor injections under local anesthesia, and will be followed for 52 weeks. Three EG110A doses (Cohorts 1-3) are being investigated. Outcome measures include treatment-emergent adverse events (AEs; primary objective), UI episodes, urodynamic parameters (eg, maximum cystometric capacity), and patient-reported outcomes (eg, Incontinence Quality of Life questionnaire). We are presenting data from Cohort 1 (EG110A dose, 1×10^8  plaque-forming units) through Week 36.

Four participants were enrolled in Cohort 1, with a mean (SD) age of 39.8 (13.2) years, 3 males. One participant was lost to follow-up after Week 8 (nonmedical reason). All participants demonstrated a clinically relevant and consistent reduction in UI episodes at Week 4 (first observation) through Week 36. The mean number of UI episodes per week decreased from 26.3 at baseline to 2.7 at Week 12 (88.3% mean percentage decrease), with sustained effects observed at Weeks 24 and 36. Improvements from baseline in urodynamic parameters and patient-reported outcomes were also observed. The most frequently reported AEs were nausea (n=2) and pyrexia (fever; n=2), which occurred in the 24-hour post-injection period. Most AEs were mild in intensity. Cohort 2 enrollment is ongoing.

A novel gene therapy designed to selectively silence type C sensory neurons of the bladder wall reduces clinical signs and symptoms of NDO and UI in adults with SCI.

In this study, the first evaluated dose of EG110A was well tolerated in adults with SCI who had NDO and UI, with clinically meaningful reductions in the number of UI episodes starting at Week 4 and continuing throughout Week 36.