Regeneron’s DB-OTO Gene Therapy Shows Promising Hearing Improvements In Trial

Regeneron Pharmaceuticals, Inc. has shared updated findings from its Phase 1/2 CHORD trial on DB-OTO, an investigational gene therapy for children with profound hearing loss caused by otoferlin (OTOF) gene mutations. The results, presented at the Association for Research in Otolaryngology’s (ARO) 48th Annual MidWinter Meeting, include 72-week data from the first child treated at 10 months of age and initial results from 11 other participants aged 10 months to 16 years. In total, 12 children received DB-OTO, nine in one ear and three bilaterally, through an intracochlear injection, a surgical approach similar to cochlear implantation that allows early intervention in infants.

Jay T. Rubinstein, M.D., Ph.D., Virginia Merrill Bloedel Professor of Otolaryngology and Bioengineering and Director, Bloedel Hearing Research Center, University of Washington School of Medicine, and a CHORD clinical trial investigator, said in a statement, “Sound is a significant part of the human experience that connects us and our environment. 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 the other ear was removed. These seemingly small interactions are life-changing for these children and their families, and these results continue to underscore the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related hearing loss.”

Findings from the first treated child show hearing improvement to near-normal levels in key speech frequencies, with positive auditory brainstem responses (ABRs) and successful word identification without visual cues at 72 weeks. Among the 11 other participants, 10 showed improved hearing at various decibel levels, with three achieving nearly normal or normal hearing at 24 weeks. Hearing improvements were confirmed by pure tone audiometry (PTA) and ABR responses. The procedure and DB-OTO were well tolerated, with no serious treatment-related adverse events. Five participants had temporary post-surgical vestibular issues that were resolved within six days. DB-OTO has received multiple FDA designations, including Orphan Drug and Fast Track, and is still under clinical investigation.