TARRYTOWN, NEW YORK – Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced updated data from the Phase 1/2 CHORD trial evaluating the investigational gene therapy DB-OTO in children with profound genetic hearing loss caused by otoferlin (OTOF) gene variants.
The latest findings, presented at the Association for Research in Otolaryngology’s (ARO) 48th Annual MidWinter Meeting, include 72-week results showing speech and developmental progress in the first child treated at 10 months of age and initial hearing improvements in 10 of 11 children with at least one post-treatment assessment. Three of these children received DB-OTO bilaterally (in both ears).
“Sound is a significant part of the human experience that connects us to each other and our environment,” said 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.
“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.”
–Jay T. Rubinstein, M.D., Ph.D
Key Findings from the CHORD Trial
The CHORD trial has enrolled 12 children to date, with nine receiving an intracochlear injection in one ear and three receiving bilateral treatment. The surgical procedure closely resembles cochlear implantation, making it feasible for use in young infants.
At 48 weeks post-treatment, the first child dosed in the trial showed hearing improvement to near-normal levels across key speech frequencies. Speech perception tests conducted at week 72 demonstrated continued improvement, with the child correctly identifying words—such as mommy, cookies, and airplane—at conversational levels without visual cues.
Among the 11 children with at least one post-treatment assessment:
- 10 demonstrated a meaningful response, with improved hearing at various decibel hearing levels (dBHL).
- Of the five children with 24-week assessments, three experienced hearing threshold improvements to “nearly normal” (≤40 dBHL) or normal (≤25 dBHL) levels.
- Hearing improvements assessed by pure tone audiometry (PTA) were corroborated by auditory brainstem response (ABR) testing.
One participant has not shown hearing changes from baseline at 24 weeks post-dosing.
Safety and Tolerability
DB-OTO has been well tolerated across all 12 participants, with no serious adverse events related to the therapy. The most common transient post-surgical vestibular side effects (such as nystagmus, nausea, dizziness, and vomiting) resolved within six days of dosing.
Regulatory Status
DB-OTO has received:
- Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the U.S. Food and Drug Administration (FDA).
- Orphan Drug Designation from the European Medicines Agency (EMA).
DB-OTO is currently under clinical investigation, and its safety and efficacy have not yet been evaluated by any regulatory authority.
About Otoferlin-related Hearing Loss
Congenital deafness affects approximately 1.7 out of every 1,000 newborns in the U.S., with nearly half of cases attributed to genetic causes. Otoferlin-related hearing loss is a rare subtype, caused by mutations in the OTOF gene, which prevent the production of functional otoferlin protein—a critical component for inner ear sensory cell communication with the auditory nerve.
About the CHORD Trial
The CHORD trial is an ongoing Phase 1/2, first-in-human, multicenter, open-label trial evaluating the safety, tolerability, and preliminary efficacy of DB-OTO in infants, children, and adolescents with otoferlin-related hearing loss.
Currently enrolling participants in the U.S., United Kingdom, and Spain (<18 years old), the trial consists of two parts:
- Part A: Dose-escalation cohort, where participants receive a single intracochlear injection in one ear.
- Part B: Expansion cohort, where participants receive bilateral injections at the selected dose.
Hearing improvements are assessed using PTA (pure tone audiometry) and ABR (auditory brainstem response) testing. At baseline, all participants had no detectable hearing responses at maximum sound levels (≥100 dB).
For more information, including trial enrollment, contact [email protected].
About DB-OTO and Regeneron’s Auditory Program
DB-OTO is an investigational gene therapy designed to restore hearing in individuals with OTOF gene mutations. Delivered via intracochlear injection, it uses a dual adeno-associated virus (AAV) vector to introduce a functional OTOF gene under the control of a proprietary, inner hair cell-specific Myo15 promoter.
Beyond DB-OTO, Regeneron is investigating additional gene therapy targets for genetic forms of hearing loss, including GJB2-related hearing loss.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company dedicated to developing life-transforming medicines for serious diseases, including genetic hearing loss, eye diseases, cancer, cardiovascular and metabolic diseases, infectious diseases, and rare conditions.
Through proprietary technologies such as VelociSuite® and Regeneron Genetics Center®, the company pioneers next-generation therapies to advance the field of genetic medicine.
**Interested to learn the latest in hearing loss therapeutic development? Check out this panel session from the 2025 Hearing Therapeutics Summit:
Source: Regeneron
