Pune, India | October 15, 2025
In a groundbreaking advancement, Regeneron’s experimental gene therapy DB-OTO has successfully restored hearing in children born with complete deafness. Previously, experts believed that mutations in the OTOF gene led to permanent hearing loss from birth. However, early results from Regeneron’s Phase 1/2 CHORD trial now challenge that long-standing belief.
Researchers have, for the first time, demonstrated that targeted gene therapy can enable natural hearing in children with profound genetic deafness. The CHORD trial enrolled twelve children between the ages of ten months and sixteen years, all of whom had mutations in both copies of the OTOF gene. During the trial, nine children received DB-OTO in one ear, while three underwent treatment in both ears through a single-dose surgical procedure.
Importantly, doctors delivered the therapy directly into the cochlea. Within weeks of treatment, eleven of the twelve children experienced meaningful improvements in hearing, and in several cases, progress continued to build over time. Notably, three children achieved hearing sensitivity within normal ranges, while six others were able to hear soft speech without requiring cochlear implants or visual cues.
One child who initially failed to meet the hearing improvement goal showed notable recovery by the 48-week checkup. Among the eight participants monitored for at least 36 weeks, hearing improvements either remained steady or continued to advance. This demonstrates the treatment’s potential for lasting and even progressive benefits.
To evaluate speech comprehension, researchers conducted word and phrase recognition tests with three children who had gained hearing. Encouragingly, all three exhibited noticeable improvements. One child identified words such as “airplane,” “cookies,” and “mommy” without relying on subtitles or lip-reading. Moreover, this child responded to distant sounds in noisy environments, showing signs of real-world auditory function.
According to Regeneron, DB-OTO addresses a critical unmet need for children with biallelic OTOF mutations. Traditionally, these children rely on cochlear implants, which electronically stimulate the auditory nerve. In contrast, DB-OTO allows the ear to process sounds naturally, potentially offering improved sound localization and overall hearing quality.
Equally significant, the therapy demonstrated a favorable safety profile throughout the trial. Most side effects were mild and temporary. Only two serious adverse events occurred — one related to a previous cochlear implant procedure and another from a standard vaccination. Neither case was directly linked to the DB-OTO treatment itself.
Some children experienced brief dizziness or nausea after surgery, likely due to inner ear disturbance. Fortunately, these symptoms resolved within a few days, and no long-term complications were observed. This safety record further supports the therapy’s viability for broader clinical use.
The trial achieved its primary endpoint by 24 weeks. Nine children reached hearing thresholds of 70 decibels hearing level (dBHL) or better, a range in which hearing aids or implants may not be necessary. Brainstem response testing confirmed these results for most participants, underscoring the therapy’s measurable clinical effectiveness.
Another key milestone came when the first child treated with DB-OTO reached 72 weeks post-treatment. That child demonstrated strong speech development and consistently recognized spoken words, showing a profound change in communication ability. The improvement marked a life-altering transformation and highlighted the therapy’s long-term promise.
Looking ahead, Regeneron plans to submit a regulatory application for DB-OTO to the U.S. Food and Drug Administration (FDA) by the end of 2025. Notably, DB-OTO has already received multiple designations, including Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy (RMAT). These designations may accelerate the approval process and help bring the therapy to more patients.
Currently, the CHORD trial remains open in the United States, the United Kingdom, Spain, and Germany. Researchers aim to treat additional patients under 18, gathering more data on both safety and effectiveness.
In parallel, Regeneron is also progressing with gene therapies for STRC and GJB2 mutations, which are other common causes of inherited deafness. These efforts align with the company’s broader mission to transform auditory healthcare using precision medicine.
Until now, children born without otoferlin faced a silent world with no natural sound. Today, thanks to DB-OTO, that silence is being replaced by voices, laughter, and music. This achievement marks not just a medical breakthrough but a hopeful turning point for families affected by congenital hearing loss. For the first time, restoring natural hearing in genetically deaf children is no longer a distant dream — it’s an emerging medical reality.
