French biotech EG 427 has achieved promising results with its herpes simplex virus (HSV)-based gene therapy EG110A, demonstrating an over 88% reduction in urinary incontinence episodes in patients with neurogenic detrusor overactivity (NDO) by week 12 of a Phase Ib/IIa trial. The therapeutic effect was clearly established as early as week four, marking a significant milestone for the company's innovative approach to treating this debilitating condition.
Trial Results and Safety Profile
In the Phase Ib/IIa trial (NCT06596291), the lowest dose of EG110A showed remarkable efficacy in reducing urinary incontinence episodes by more than 80% overall, with the most significant reduction reaching over 88% by week 12. The drug is being investigated specifically for treating NDO in people with spinal cord injury (SCI), where urinary incontinence represents the primary symptom.
The company reported that EG110A demonstrated a good safety profile throughout the study, providing confidence for continued development. Following these positive results, dosing in the second cohort has commenced, indicating the trial's progression to evaluate additional dose levels.
Mechanism of Action and Treatment Approach
EG110A represents a novel therapeutic approach utilizing a non-replicating HSV-1 vector designed to selectively silence the signals of type C sensory neurons responsible for bladder muscle overactivity. Critically, the therapy preserves other bladder controls, maintaining normal bladder function while addressing the pathological overactivity that causes incontinence.
Patients receive a single treatment course consisting of multiple intradetrusor injections, offering the potential for long-lasting therapeutic benefit from a single intervention. This approach contrasts significantly with current standard treatments that require ongoing administration.
Platform Validation and Future Applications
EG 427 CEO Dr Philippe Chambon emphasized the broader implications of these results, stating: "For EG 427, as these validate a biological mechanism underpinning multiple diseases driven by type C sensory neuron activity, we can now envision developing EG110A more broadly in clinical studies in multiple underserved pathologies, including in the pain field."
The success validates the company's proprietary HERMES nrHSV-1 technology platform, which has been used to discover EG142A and two other disclosed therapies. This platform approach suggests potential applications beyond urological conditions, particularly in pain management where type C sensory neurons play crucial roles.
Disease Burden and Current Treatment Landscape
NDO represents a significant medical challenge, affecting at least two million patients suffering from SCI, multiple sclerosis (MS), Parkinson's disease, and other neurodegenerative diseases across the seven major markets (US, France, Germany, Italy, Spain, UK, and Japan). The condition causes uncontrolled urinary incontinence and carries serious risks including kidney damage and urinary tract infections (UTIs) that can prove fatal in 5-10% of the SCI population.
Current standard of care for patients with NDO includes anticholinergic medications and intermittent catheterization (CIC). When these first-line therapies prove unsuccessful, patients may receive botulinum toxin A (BTX-A) injections or undergo bladder augmentation, a surgical procedure involving enlarging the bladder with a segment of bowel.
Gene Therapy Precedent
EG 427 joins a growing field of companies developing non-replicating herpes vector products. In 2023, Krystal Biotech received FDA approval for its gene therapy Vyjuvek to treat dystrophic epidermolysis bullosa (DEB), demonstrating the regulatory pathway's viability for HSV-based gene therapies.
The promising Phase Ib/IIa results position EG110A as a potential breakthrough treatment for NDO patients who currently face limited therapeutic options and significant quality-of-life impacts from their condition.
