Regeneron’s AAV Gene Therapy Restores Hearing in Most Children with Profound Genetic Deafness

INDIANAPOLIS – October 14, 2025 – A single infusion of the investigational gene therapy DB-OTO successfully restored hearing in most children with congenital profound deafness caused by mutations in the OTOF gene, according to results from the pivotal Phase I/II CHORD study. The data was reported by developer Regeneron Pharmaceuticals and colleagues in the New England Journal of Medicine and presented at the American Academy of Otolaryngology-Head and Neck Surgery meeting.

DB-OTO Enables Functional Hearing
Of 12 children treated with the dual AAV (Adeno-associated virus)-based gene therapy, 11 achieved clinically meaningful hearing improvements. DB-OTO delivers the large genomic payload needed to correct the defect in the otoferlin protein (encoded by the OTOF gene), which is essential for synaptic transmission in the inner ear.

Key efficacy findings at 24 weeks post-treatment:

75% (9 of 12 participants) met the primary endpoint, achieving a hearing threshold of 70 dB HL or less, a level that generally avoids the need for cochlear implants. None of the untreated ears showed improvement.

50% (6 participants) reached 45 dB HL sensitivity or better, enabling them to hear soft speech unaided.

25% (3 participants) attained a normal hearing sensitivity of 25 dB HL or less, allowing them to hear a whisper.

Lawrence R. Lustig, M.D., a co-author from Columbia University, stated, “This truly represents a new era in the treatment of hearing loss,” noting that OTOF-related hearing loss was previously considered permanent, treatable only with cochlear implants.

Benefits Observed Across Ages
The study surprisingly observed benefits when DB-OTO was administered to participants as old as 16 years of age, challenging the prevailing view that gene therapy efficacy might be limited to early life intervention. Nevertheless, all three participants who completed speech assessments showed significant improvement, highlighting the importance of early treatment for language development.

The DB-OTO therapy is delivered locally as a single intracochlear infusion. Researchers anticipate a durable clinical benefit after a single infusion because the targeted inner hair cells are terminally differentiated, meaning the introduced gene should not be diluted through cell replication.

The gene therapy holds Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the FDA and is expected to be submitted for New Drug Approval later this year.