TARRYTOWN, N.Y. — October 12, 2025 — Leads & Copy — Regeneron Pharmaceuticals, Inc. announced updated data for its investigational gene therapy DB-OTO, which targets profound genetic hearing loss due to variants of the otoferlin (OTOF) gene. The data, published in The New England Journal of Medicine and presented at the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNSF) meeting, revealed that 11 out of 12 participants in the pivotal CHORD trial experienced clinically meaningful hearing improvements, including three who achieved normal hearing levels.
Eight participants with longer follow-up showed stability or continued improvement in their hearing. All three participants who completed speech assessments demonstrated significant improvement, with one able to identify one- and two-syllable words without visual cues and respond to distant sounds and speech in noisy environments.
The CHORD trial evaluated pediatric participants with profound hearing loss due to OTOF gene variants, who received a single administration of DB-OTO via intracochlear infusion. Nine of the 12 participants (aged 10 months to 16 years) received the gene therapy unilaterally, and three received it bilaterally. The surgical procedure is similar to cochlear implantation.
The trial met its primary endpoint, with nine participants experiencing hearing improvements at a threshold of ≤70 decibel hearing level (dBHL) at week 24. Six participants could hear soft speech without assistive devices, and three could detect whispers, achieving normal hearing sensitivity. One participant who did not meet the primary endpoint at week 24 improved to achieve “nearly normal” hearing sensitivity at week 48. Nine participants also demonstrated an auditory brainstem response (ABR) at ≤90 decibels (dB), achieving the trial’s key secondary endpoint.
Hearing improvements remained stable or continued to improve in eight participants with follow-up visits of ≥36 weeks (up to 72 weeks). Across all 12 participants, both the surgical procedure and DB-OTO were well tolerated, and there were no DB-OTO-related adverse findings reported.
The U.S. regulatory application for DB-OTO is planned for later this year, pending discussions with the U.S. Food and Drug Administration (FDA). DB-OTO has received Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the FDA, as well as Orphan Drug Designation from the European Medicines Agency.
Contacts:
Tammy Allen
Tel: +1 914-306-2698
tammy.allen@regeneron.com
Mark Hudson
Tel: +1 914-847-3482
mark.hudson@regeneron.com
Source: Regeneron
