Trial launches of gene therapy vector for neurogenic bladder due to spinal cord injury

A phase 1b/2a trial (NCT06596291) has been initiated to evaluate the safety, tolerability, and initial efficacy of the non-multiplying gene therapy vector EG110A as a treatment for patients with neurogenic bladder-related incontinence following a spinal cord injury.^1.2

EG110A was shown to last for several years in preclinical studies.

The first patient in the trial was dosed at Rancho Research Institute of Rancho Los Amigos National Rehabilitation Center in the greater Los Angeles area. The trial is taking place across 4 centers in the US, including the one in California as well as in Michigan, Pennsylvania, and Texas.

According to EG 427, the developer of the therapy, “EG110A is a non-replicating HSV-1 vector that has been designed to selectively silence the signals of key bladder sensory neurons responsible for the bladder muscle overactivity, whilst preserving motor neuron and retaining normal bladder function.”

“They have modified the herpes virus, which affects nerves, so that it is not virulent and does not multiply, and are relying on its innate ability to travel along nerve cells and reside in the sensory cells by the spinal cord,” explained lead investigator of the Houston site Argyrios Stampas, MD, MS, in the news release.² “Once the vector is in place, it will manufacture its medication. It will block the sensory signals in the spinal cord that cause reflexive bladder contractions. This is the science fiction stuff that I dreamed about as an undergrad.”

Compared with the current standard treatment for neurogenic bladder, which requires multiple injections every 6 months, EG110A was shown to last for several years in preclinical studies.

“When people living with spinal cord injury are surveyed, bowel and bladder issues are their top priority,” added Stampas, an associate professor of physical medicine and rehabilitation in McGovern Medical School at UTHealth Houston and director of Spinal Cord Injury Medicine Research at TIRR Memorial Hermann. “The opportunity to have one procedure that could relieve incontinence for years would be a huge improvement on their quality of life.”

In total, the 52-week dose-escalation study plans to enroll 16 adult patients with neurogenic bladder due to a spinal cord injury that occurred at least 12 months before study screening. To be eligible for enrollment, patients must be aged 18 to 75, have persistent urinary incontinence after standard of care therapy, and must perform clean intermittent catheterization on a regular basis.

According to EG 427, those enrolled in the study will receive “a single treatment course consisting of multiple intradetrusor injections of EG110A.” EG110A will be administered across 3 dose levels (low, medium, and high) to determine the recommended dose level for further assessment.³

The primary outcome measure is the incidence of treatment-emergent adverse events.Secondary outcome measures include the change in urodynamic variable from baseline to weeks 12 and 52 as well as outcomes from a 7-day bladder diary, which will record urinary incontinence episodes, daily catheterization rates, and volume per catheterization.

The study also includes a 5-year safety follow-up period.

REFERENCES

1. Significant milestone reached for EG 427 with first patient treated with EG110A, first non-replicative herpes vector based genetic medicine for the treatment of neurogenic bladder. News release. EG 427. February 27, 2025. Accessed March 14, 2025. https://eg427.com/First-Patient-EG110A.html

2. New clinical trial at UTHealth Houston tests gene therapy vector that delivers drug aimed at stopping overactive bladder in patients with spinal cord injury. News release. University of Texas Health Science Center at Houston. March 12, 2025. Accessed March 14, 2025. https://www.newswise.com/articles/new-clinical-trial-at-uthealth-houston-tests-gene-therapy-vector-that-delivers-drug-aimed-at-stopping-overactive-bladder-in-patients-with-spinal-cord-injury

3. Dose escalation study of EG110A, administered by intradetrusor injections to adults with neurogenic detrusor overactivity-related incontinence following spinal cord injury who regularly perform clean intermittent catheterization. ClinicalTrials.gov. Last updated February 11, 2025. Accessed March 14, 2025. https://clinicaltrials.gov/study/NCT06596291