Efficacy and Safety of DB-OTO Gene Therapy in Pediatric Patients with Profound Hearing Loss

Sunday, October 12, 2025

10:18 AM - 10:24 AM EDT

Location: 244

Disclosure(s):

Lawrence R. Lustig, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Introduction: Otoferlin plays a crucial role in inner hair cell (IHC) signal transmission to auditory nerve fibers; however, pathogenic variants in the otoferlin gene (OTOF), in most cases, result in severe-to-profound hearing loss (HL). Preclinical studies indicate that DB-OTO, an adeno-associated virus gene therapy which drives IHC-specific expression of otoferlin from human OTOF, may restore high-quality hearing. The CHORD study (NCT05788536) is an ongoing trial evaluating the safety and efficacy of DB-OTO in pediatric participants with profound HL.

Methods: Eligible participants ( < 18 years of age) had biallelic pathogenic or likely pathogenic variants in OTOF with profound HL by behavioral pure tone audiometry and no detectable response on auditory brainstem response testing at maximum stimulus levels. Participants received an intracochlear injection of DB-OTO (7.2 x 1012 vector genomes), unilaterally or bilaterally, via the round window. Safety and efficacy measurements were performed at multiple timepoints pre- and post-treatment.

Results: Early safety and efficacy data have been shared previously. To date, surgical delivery has been uneventful in all participants. No dose-limiting toxicities or DB-OTO–related adverse events have been reported, and no persistent vestibular manifestations have been observed. Updated data from the trial, including long-term data and early speech assessments from the first participant, and initial data from bilaterally dosed patients will be presented at this meeting.

Conclusions: These encouraging data suggest that DB-OTO has the potential to enable physiological hearing in children with otoferlin deficiency, and is well tolerated.

Presenting Author(s)

LL

Lawrence R. Lustig, MD

Howard W. Smith Professor and Chair
Dep't Otolaryngology, Columbia University Medical Center
New York, NY, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Senior Author(s)

LL

Lawrence R. Lustig, MD

Howard W. Smith Professor and Chair
Dep't Otolaryngology, Columbia University Medical Center
New York, NY, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Co-Author(s)

Manohar L. Bance, n/a

Professor of Otology and Skull Base Surgery
Cambridge University
Cambridge, United States

Disclosure information not submitted.
JR

Jay T T. Rubinstein

Virginia Merrill Bloedel Professor and Director
University of Washington
Seattle, WA, United States

Disclosure information not submitted.
Akira Ishiyama, MD

Professor of Otolaryngology-Head and Neck Surgery
UCLA School of Medicine
Los Angeles, CA, United States

Disclosure information not submitted.
RN

Robert Nash, n/a

Great Ormond Street Hospital, United States

Disclosure information not submitted.
RP

Ruben Polo, n/a

Hospital Universitario Ramon y Cajal, United States

Disclosure information not submitted.
MM

Manuel Jesus Manrique, n/a

Clinica Universidad de Navarra, United States

Disclosure information not submitted.
Evie C. Landry, MD, MSc, FRCSC, FAAP

Pediatric Otolaryngology - Head & Neck Surgery
Nemours Children's Health
Jacksonville, FL, United States

Disclosure information not submitted.
TQ

Tera M. Quigley, AuD

Clinical Scientist
Regeneron Pharmaceuticals, Inc.
East Boston, MA, United States

Disclosure information not submitted.
JR

Jason Riggs, n/a

Regeneron Pharmaceuticals, Inc., United States

Disclosure information not submitted.
EC

Eduardo Corrales, n/a

Regeneron Pharmaceuticals, Inc., United States

Disclosure information not submitted.
JW

Jonathon P. Whitton, AuD, PhD

Vice President
Regeneron Pharmaceuticals, Inc.
South Salem, NY, United States

Disclosure information not submitted.
JA

Jeffery Anderson, n/a

Regeneron Pharmaceuticals, Inc., United States

Disclosure information not submitted.
VV

Vassili Valayannopoulos

Executive Director, Clinical Program Lead
Regeneron Pharmaceuticals, Inc.
Boston, MA, United States

Disclosure information not submitted.