Mursalin Pathan – Content Writer
Pune, India | October 15, 2025
Regeneron’s gene therapy DB-OTO achieved a groundbreaking success by restoring hearing in children born completely deaf. Previously, doctors believed mutations in the OTOF gene caused irreversible hearing loss from birth onward. Yet, Phase 1/2 results from Regeneron’s CHORD trial now challenge this belief. For the first time, targeted gene therapy helped children with profound genetic hearing loss regain natural hearing.
The trial involved twelve children aged from ten months to sixteen years, all carrying mutations on both copies of the OTOF gene. Nine of these children had DB-OTO delivered to one ear, while three received it in both ears surgically. Importantly, the therapy was administered in a single dose directly into the cochlea.
Remarkably, eleven children showed significant hearing improvements within weeks of treatment, with gains continuing over time. Of those, three regained normal hearing sensitivity, and six began detecting soft speech without any help from visual cues or cochlear implants. One child, initially not meeting improvement targets, showed substantial progress by the 48-week follow-up.
Among the eight children monitored for 36 weeks or more, hearing improvements either stabilized or continued to improve. Researchers also assessed speech recognition in three children who had better hearing by conducting word and phrase identification tests. Encouragingly, all three made notable progress. One child could identify words such as “airplane,” “cookies,” and “mommy” without relying on lip-reading or subtitles. Furthermore, this child responded to distant sounds amid noise, indicating improved real-world listening ability.
Regeneron emphasized that DB-OTO addresses a vital unmet need among children with biallelic OTOF mutations, who typically require cochlear implants. Unlike implants, which provide sound electronically, this gene therapy allows natural sound processing in the ear. This advancement potentially leads to better sound localization and a higher quality of life.
The therapy’s safety profile also proved encouraging. Most side effects were mild or temporary. Only two serious adverse events occurred: one related to a previous cochlear implant and another due to a routine vaccination, neither linked to DB-OTO treatment. Some children experienced short-term dizziness or nausea after surgery, likely from inner ear disturbance, but these symptoms resolved within days without long-term effects. This favorable safety data further supports DB-OTO’s promise.
Importantly, the trial met its primary endpoint. By 24 weeks, nine children achieved hearing thresholds of 70 dBHL or lower. At this level, hearing aids or implants may not be necessary. Additionally, brainstem response tests confirmed the hearing gains in most participants.
In another milestone, the first child treated with DB-OTO recently reached 72 weeks post-treatment, demonstrating remarkable speech and developmental progress. This child identified common words and consistently engaged with sounds in daily life—a truly life-changing transformation.
Looking ahead, Regeneron plans to submit a regulatory application for DB-OTO to the U.S. Food and Drug Administration by the end of 2025. The therapy has earned multiple designations, including Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy (RMAT). These recognitions could accelerate its approval and broaden access for affected children.
The CHORD trial is still enrolling participants in the United States, the United Kingdom, Spain, and Germany. Researchers aim to treat more children under 18, further refining DB-OTO’s safety and effectiveness.
Alongside DB-OTO, Regeneron is advancing gene therapy programs targeting STRC and GJB2 gene mutations, also common causes of inherited hearing loss. These efforts align with the company’s vision of transforming auditory medicine through precision gene therapies.
Until now, children born without otoferlin faced life without natural sound. Thanks to DB-OTO, voices, laughter, and music may become a part of their lives. This breakthrough marks a historic moment for gene therapy and millions of families affected by congenital deafness. Restoring natural hearing in genetically deaf children is now an achievable medical reality on the horizon.
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