DB-OTO Gene Therapy in Children with Profound Hearing Loss: CHORD Trial Early Speech Results

Monday, October 19, 2026

8:54 AM - 9:00 AM PT

Location: 511AC

Presenting Author(s)

JG

John H. Greinwald Jr., MD

Dr
Cincinnati Children's Hospital, University of Cincinnati, United States

Co-Author(s)

LL

Lawrence R. Lustig, MD

Professor and Chair
Columbia University Irving Medical Center
New York, New York, United States
SH

Steven A. Harvey, MD

Dr
Medical College of Wisconsin, United States
TQ

Tera M. Quigley, AuD

Dr
Regeneron Pharmaceuticals, Inc.
East Boston, MA, United States
CC

C. Eduardo Corrales, MD

Dr
Regeneron Pharmaceuticals, Inc., United States
JW

Jonathon P. Whitton, AuD, PhD

Professor
Regeneron Pharmaceuticals, Inc.
South Salem, NY, United States

Senior Author(s)

VV

Vassili Valayannopoulos on behalf of the CHORD study group, MD, PhD

Executive Director
Regeneron Pharmaceuticals, Inc.
Cambridge, Massachusetts, United States

Introduction: DB-OTO, a dual adeno-associated virus 1 gene therapy, was designed to enable hearing in individuals with otoferlin-related deafness. The CHORD trial is evaluating the safety and efficacy of DB-OTO in pediatric participants with congenital deafness.

Methods: Eligible participants ( < 18 years of age) from the ongoing CHORD trial (NCT05788536) with biallelic pathogenic or likely pathogenic variants in the otoferlin gene (OTOF) and profound deafness received an intracochlear infusion of DB-OTO (7.2 x 10^12 vector genomes/ear), unilaterally or bilaterally. Safety and efficacy measurements were performed at multiple timepoints pre- and post-treatment. Hearing sensitivity was assessed by pure tone audiometry and Auditory Brainstem Response. Speech perception abilities were evaluated using clinician and caregiver Global Impression Scales, the LittlEARS questionnaire, and the Auditory Skills Checklist (ASC).

Results: Efficacy and safety results from 12 participants in the trial have been previously shared. After DB-OTO infusion, 9/12 (75%) participants had significant improvement in hearing at 24 weeks. These 12 participants were followed over 48 weeks and assessed for speech and language outcomes. At Week 48, 10 participants completed Global Impression Scales with 6/9 and 6/10 participants having much improved or very much improved speech perception by clinician and caregiver ratings, respectively. Most participants who showed improved hearing sensitivity also had rapid gains in LittlEARS questionnaire scores and/or ASC scores when available. No DB-OTO–related adverse reactions were reported.

Conclusions: These data suggest that DB-OTO safely enables hearing that translates into favorable speech outcomes in children with OTOF-related deafness.