HQ Team
February 25, 2025: Regeneron Pharmaceuticals, Inc.’s investigational gene therapy improved hearing in 10 out of 11 children born with hearing loss because of gene mutation, according to a company statement.
The initial and mid-stage trials for the therapy named DB-OTO included children from 10 months to 16 years.
The treatment aims to deliver a working copy to replace the faulty OTOF gene using a modified, non-pathogenic virus that is delivered through an injection into the cochlea under general anaesthesia.
Otoferlin-related hearing loss is ultra-rare.
This specific condition is caused by variants in the OTOF gene, which leads to a lack of a functional otoferlin protein that is critical for the communication between the sensory cells of the inner ear and the auditory nerve.
‘Nearly normal’
Among the 11 participants with at least one post-treatment assessment, 10 demonstrated “a notable response, with improved hearing at various decibel hearing levels.”
Additionally, among five participants with 24-week assessments, three experienced improvements in average hearing thresholds to “nearly normal” hearing levels.
Auditory brainstem responses were corroborated by hearing improvements assessed by pure tone audiometry, according to the statement.
One participant did not experience a change from their baseline hearing at 24 weeks post-dosing.
The latest results were presented in an oral presentation at the ongoing Association for Research in Otolaryngology’s (ARO) 48th Annual MidWinter Meeting.
Mommy, cookies, aeroplane
The 48-week results from the first participant dosed in the trial showed an improvement in hearing to near-normal levels across key speech frequencies.
This included hearing thresholds that were within normal limits in most speech-relevant frequencies and corroborated with positive auditory brainstem responses.
Particularly encouraging were results from formal speech perception tests in which the child demonstrated improvement from week 48 to week 72 and correctly identified words – such as mommy, cookies and aeroplane – that were presented at a conversational level without any visual cues.
“Sound is a significant part of the human experience that connects us to each other and our environment,” said Jay T. Rubinstein, MD, PhD, Virginia Merrill Bloedel Professor of Otolaryngology and Bioengineering and Director, Bloedel Hearing Research Center, University of Washington School of Medicine, and a 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.”
No serious adverse events
Both the surgical procedure and DB-OTO were well tolerated, and there were no adverse events or serious adverse events considered related to DB-OTO, according to the statement.
Five of the participants experienced transient post-surgical vestibular adverse events (e.g., nystagmus, nausea, dizziness, vomiting), which resolved within six days of dosing.
DB-OTO received Orphan Drug, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy designations from the US Food and Drug Administration and Orphan Drug Designation was granted by the European Medicines Agency.
The potential use of DB-OTO for otoferlin-related hearing loss is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.
Congenital deafness or hearing loss present at birth, is a significant unmet medical need that affects approximately 1.7 out of every 1,000 children born in the US and approximately half of these cases have genetic causes.
