Breakthrough in Gene Therapy: Regeneron's DB-OTO Restores Hearing in Children with Congenital Deafness

The field of biotechnology has recently witnessed a major breakthrough concerning DB-OTO, an experimental gene therapy developed by Regeneron Pharmaceuticals. This innovative treatment is specifically designed to address the profound congenital deafness resulting from mutations in the OTOF gene, offering the genuine potential to restore natural acoustic hearing.

Highly encouraging data emerged from the Phase I/II CHORD study. This clinical investigation involved twelve pediatric participants, ranging in age from 10 months to 16 years. The findings were presented at the annual meeting of the American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO-HNSF) and simultaneously published in the esteemed journal The New England Journal of Medicine.

The study demonstrated that the therapy, which functions by utilizing a dual-vector adeno-associated virus (AAV) to deliver a functional copy of the OTOF gene, successfully led to the recovery of natural acoustic perception in the majority of the children enrolled in the trial.

By the 24-week evaluation point, nine out of the twelve children had achieved hearing thresholds categorized as moderate or normal. This significant level of recovery typically negates the necessity for cochlear implantation, representing a massive improvement in quality of life. Furthermore, three specific participants demonstrated an almost complete restoration of their auditory function.

DB-OTO is administered via an intracochlear injection, a procedure similar to that used for placing cochlear implants. This delivery method makes the therapy viable even for the youngest patients. Improvements in hearing were observed just weeks following the injection. Significant progress in speech recognition and the ability to respond to quiet sounds in noisy environments were documented in three children who underwent speech assessments at the 48-week follow-up.

Crucially, the therapy appears to be well-tolerated, as no serious adverse events directly attributable to DB-OTO were recorded during the study period. While the OTOF mutation accounts for an estimated 2–8 percent of all congenital genetic deafness cases, this breakthrough represents a pivotal moment in the treatment landscape for inherited forms of hearing loss.

Looking ahead, Regeneron intends to submit a Biologics License Application (BLA) to the FDA before the close of 2025. Experts suggest that successfully treating this specific defect could act as a powerful catalyst for developing corrective methods targeting more prevalent genetic mutations, such as GJB2. This success fundamentally shifts the focus of otology toward restoring the ear's inherent natural mechanisms for hearing, rather than relying solely on external devices.