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Scientific Oral Presentations

Pediatric Otolaryngology

Session: Scientific Oral Presentations 4 - Pediatric Otolaryngology

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

Sunday, September 29, 2024
3:12 PM – 3:18 PM EDT
Location: MBCC, 225
Disclosure(s):
Carleton E. Corrales, MD:

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

Manohar L. Bance, MB, ChB, MSc, FRCS, FRCSC, ABOto:

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

Lawrence R. Lustig, MD:

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

Introduction: Otoferlin is critical for inner hair cell (IHC) signal transmission to afferent auditory nerve fibres. Biallelic otoferlin gene (OTOF) mutations typically cause severe to profound hearing loss (HL). As per preclinical data, DB-OTO gene therapy promotes IHC-selective expression of otoferlin from the human OTOF gene, which may instate high-quality hearing. In this first-in-human study, safety and preliminary efficacy of DB-OTO in pediatric patients with profound HL are evaluated.

Methods: In this ongoing, phase 1/2 trial (CHORD, NCT05788536), patients under 18 years old (including infants ≤2 years old) from the US and UK/Spain with biallelic pathogenic OTOF variants, profound HL, otoacoustic emissions or cochlear microphonic (if >2 years) are being enrolled. A 10-month-old female, with profound OTOF-related HL at baseline (BL), received a single intracochlear DB-OTO injection (7.2x 1012 vg). DB-OTO was infused into the right inner ear perilymph via the round window using a standard facial recess approach; a cochlear implant (CI) was placed in the left ear. We present here preliminary safety and efficacy results through week 12 post-injection.

Results: DB-OTO treated ear showed measurable improvements (55 dB HL) in thresholds (behavioral audiogram) with air and bone conduction versus BL (absent thresholds at 100 dB HL, maximum air conduction intensity tested, 250–4000 Hz). Auditory brainstem response showed hearing recovery via positive wave V response with thresholds of 40–80 dB; no response reported at 100 dB at BL (500–4000 Hz). Through week 12, no dose-limiting toxicities and no DB-OTO-related adverse events were reported, including absence of vestibular manifestations. Cervical vestibular evoked myogenic potential responses through week 12 remained similar to BL. LittlEARS Auditory Questionnaire showed improvement in hearing. Additional data from this and other enrolled patients will be presented.

Conclusions: These preliminary 12-week findings suggest that DB-OTO is well-tolerated and may improve hearing in patients with profound OTOF-related HL.

    Presenting Author(s)

  • Carleton E. Corrales, MD

    Assistant Professor
    Brigham & Women's Hospital/Harvard Medical School
    Newton, MA, 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, MB, ChB, MSc

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

    Disclosure(s):

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

  • RN

    Robert Nash, BM, BCh, MA, DOHNS

    Great Ormond Street Hospital, United Kingdom

    Disclosure information not submitted.

  • MR

    Manuel Jesus Manrique Rodrigue, MD, PhD

    Clinica Universidad de Navarra, Spain

    Disclosure information not submitted.

  • RP

    Ruben Polo, MD

    Hospital Universitario Ramon y Cajal, Spain

    Disclosure information not submitted.

  • AR

    Angel M. Ramos-Macias, MD

    head ent dept
    Las Palmas University
    LAs PAlms, Canarias, Spain

    Disclosure information not submitted.

  • LL

    Lawrence R. Lustig, MD

    Professor and Chair
    Columbia University Irving Medical Center/New York Presbyterian Hospital
    New York, NY, United States

    Disclosure(s):

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

  • JR

    Jay T. Rubinstein, MD, PhD

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

    Disclosure information not submitted.

  • AI

    Akira Ishiyama, MD

    Professor, Division of Head and Neck Surgery, David Geffen School of Medicine at UCLA
    UCLA Health System, United States

    Disclosure information not submitted.

  • TQ

    Tera Quigley, AuD

    Regeneron Pharmaceuticals, Inc., United States

    Disclosure information not submitted.

  • JR

    Jason Riggs, AuD, PhD

    Regeneron Pharmaceuticals, Inc., United States

    Disclosure information not submitted.

  • JA

    Jeffrey Anderson, MD

    Regeneron Pharmaceuticals, Inc., United States

    Disclosure information not submitted.

    • Senior Author(s)

  • Vassili Valayannopoulos, MD, PhD

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

    Disclosure information not submitted.