In a good week for treating sensory disorders with gene therapy, soon after positive new gene therapy results to treat childhood blindness came out, Regeneron announced its DBO-OTO gene therapy showed ”clinically meaningful” hearing improvements in nearly all children with profound genetic hearing loss due to variants of the otoferlin (OTOF) gene. The latest results were from the potentially pivotal Phase I/II CHORD trial.
“Sound is a significant part of the human experience that connects us to each other and our environment,” said Jay T. Rubinstein, MD, PhD, director, Bloedel Hearing Research Center, University of Washington School of Medicine, and a CHORD clinical trial investigator.
“A year after treatment in one ear with DB-OTO, a child born profoundly deaf was able to enjoy music, engage in imaginative play, and participate in bedtime reading when the cochlear implant on their other ear was removed. These seemingly small interactions are life-changing for these children as well as their families and these results continue to underscore the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related hearing loss.”
Twelve participants have received DB-OTO to date—of whom nine were administered an intracochlear injection in one ear, and three received it bilaterally. Among 11 children with at least one post-treatment assessment, 10 showed notable improvements in hearing. Plus the first child treated in the trial showed speech and development progress followed by dramatic improvements in hearing at the 72-week assessment.
The Phase I/II data on DBO-OTO was presented at the Association for Research in Otolaryngology’s (ARO) 48th Annual MidWinter Meeting in Orlando, FL.
These results follow preliminary trial findings of restored hearing in two children presented last year at the American Society of Gene & Cell Therapy annual meeting. One patient returned to normal hearing levels within 24 weeks of treatment, as measured by auditory brainstem response (ABR) and the gold-standard pure tone audiometry (PTA)—both of which are validated methods of evaluating hearing function. The patient was dosed with DB-OTO at 11 months of age.
This trial is currently enrolling children across sites in the United States, the United Kingdom, and Spain (
DB-OTO is a cell-selective, dual adeno-associated virus (AAV) vector gene therapy designed to provide durable, physiological hearing to individuals with profound, congenital hearing loss caused by variants of the OTOF gene. The treatment aims to deliver a working copy to replace the faulty OTOF gene using a modified, non-pathogenic virus that is delivered via an injection into the cochlea under general anesthesia (similar to the procedure used for cochlear implantation). The newly introduced OTOF gene is under the control of a proprietary cell-specific Myo15 promoter, which is intended to restrict expression only to inner hair cells that normally express otoferlin.
In addition to OTOF, Regeneron is also investigating several other targets for genetic forms of hearing loss, including GJB2.
