First Gene Therapy for Common Neurological Diseases Gets FDA IND Clearance - EG 427 Begins Human Trials

EG 427, a biotechnology firm specializing in targeted DNA medicines for neurological diseases, announced it has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for its gene therapy product, EG110A. This therapy aims to treat Neurogenic Detrusor Overactivity (NDO) in patients with Spinal Cord Injury (SCI). The company is initiating a phase 1b/2a study at two leading institutions in the United States.

EG110A is a non-replicating HSV-1 vector designed to selectively silence key bladder sensory neurons that cause overactivity in the bladder muscle, while preserving motor neuron function and maintaining normal bladder activity. NDO is a common bladder dysfunction mainly caused by SCI and other neurodegenerative conditions like Multiple Sclerosis and Parkinson’s disease. It leads to uncontrolled urinary incontinence, potential kidney damage, and urinary tract infections, which can be fatal for 5-10% of SCI patients. NDO affects 70-84% of SCI patients, translating to an estimated 300,000-400,000 individuals globally. This condition significantly impacts their quality of life. The European Association of Urology estimates that the economic burden of incontinence caused by NDO and other conditions like overactive bladder exceeds €40 billion annually in Europe.

Cornelia Haag-Molkenteller, MD, PhD, Chief Medical Officer of EG 427, emphasized the severity of NDO and the limited treatment options available. Preclinical results show that EG110A could offer substantial medical improvements over existing therapies. One course of treatment with EG110A has the potential for long-lasting efficacy without compromising bladder function. Haag-Molkenteller expressed excitement about moving this promising product into clinical trials.

Philippe Chambon, MD, PhD, Chief Executive Officer at EG 427, highlighted the significance of the IND clearance for EG110A, marking a major milestone for the company. This approval paves the way for the clinical development of EG110A across various neuro-urology pathologies. Chambon emphasized that non-replicative HSV-1 vectors are unique in their potential to provide therapeutic solutions that are safe, redosable, and cost-effective. This step is seen as a significant advancement in bringing the benefits of gene therapy to large populations suffering from neurological diseases.

Neurological diseases affect approximately 3 billion people worldwide, or about one in three individuals, with many medical needs remaining unmet, according to a study by The Lancet Neurology. EG 427 is building a pipeline of products to address these diseases, leveraging its proprietary non-replicative HSV vector platform. This platform is uniquely suited to target neural cells safely and effectively over the long term.

EG 427 is the second company to bring a non-replicating HSV-1 (nrHSV-1) vector into clinical development, with the FDA's recent IND clearance marking a significant achievement. This will be the first human trial targeting sensory neuron-based diseases using such a vector. EG110A addresses severe bladder diseases like neurogenic bladder (NDO) and overactive bladder (OAB), potentially offering significant improvements over existing therapies in terms of patient care and cost reduction for healthcare systems.

The company’s platform delivers precise neurotherapeutics to treat prevalent diseases of the peripheral and central nervous systems. These vectors can achieve focused transduction in specific regions and selective expression of transgenes in targeted neuron subsets, thanks to sophisticated regulatory elements. With proven clinical safety and the potential for repeated dosing, nrHSV-1 vectors have a large payload capacity, allowing for either long-term gene therapy or comprehensive gene editing approaches.