DB-OTO Gene Therapy Shows Promise in Restoring Hearing
Regeneron Pharmaceuticals has released new clinical data from its gene therapy program for hereditary hearing loss, sharing updated results from the phase 1/2 CHORD trial of DB-OTO. The company is preparing for a potential FDA submission later this year.
DB-OTO is an adeno-associated virus (AAV) gene therapy originally developed by Decibel Therapeutics, which Regeneron acquired in a $109 million deal. The therapy is designed to correct a rare genetic mutation that prevents the production of a key protein needed for sound transmission through the ear’s hair cells.
Updated Trial Results
In February, Regeneron reported hearing improvement in 10 of 11 children treated with DB-OTO. The updated results, presented Sunday at the American Academy of Otolaryngology meeting, included data from 12 patients, three of whom received the treatment in both ears. At 24 weeks, nine patients achieved the trial’s primary efficacy endpoint, two demonstrated partial improvement below the hearing threshold, and one did not respond to the therapy.
The nonresponder later received a cochlear implant, the current standard of care for the condition. According to Lawrence Lustig, chair of the Department of Otolaryngology–Head and Neck Surgery at Columbia University, DB-OTO may enhance or even replace such interventions.
“When using cochlear implants, the experience is mechanical and robotic at first, but patients adjust over time,” Lustig said. “This gene therapy essentially switches the natural hearing process of the ear back on.”
Patient Progress and Long-Term Outlook
While the children in the study are too young for advanced auditory testing such as music perception, all who underwent speech assessments showed improvement. Lustig noted that their hearing function could eventually resemble that of peers without the disorder once development progresses.
Children who receive cochlear implants by 18 months and undergo speech therapy typically achieve near-normal language development, while those treated at three to four years often experience delays. Lustig highlighted a four-year-old participant in the DB-OTO study who showed unexpectedly rapid progress within 24 weeks—faster than typical cochlear implant outcomes.
The long-term durability of DB-OTO remains under evaluation. Some patients who met the primary endpoint at 24 weeks showed continued gains at week 48. However, two participants experienced high-frequency hearing decline, though this did not affect speech perception. Researchers suggested the decline could be due to uneven AAV uptake or minor hair cell damage during the procedure. Both patients later improved after steroid treatment.
Safety and Future Potential
Lustig described the surgical procedure as comparable to a cochlear implant, with only transient dizziness reported in some cases and no lasting vestibular complications. Roughly one-quarter of all adverse events occurred during or shortly after the procedure.
While one child did not respond to therapy, researchers have yet to determine the reason, though an immune response or incomplete vector delivery is suspected.
DB-OTO is intended for a rare genetic form of deafness that affects 30 to 50 children annually. Despite the limited patient population, Lustig sees the therapy as an important proof of concept for expanding genetic approaches to hearing restoration.
“I believe this will attract significant new investment into developing cures for a range of genetic deafness conditions,” he said.
Regeneron confirmed plans to seek FDA feedback and pursue a potential regulatory filing for DB-OTO later this year.
Conclusion
Regeneron’s DB-OTO gene therapy presents a compelling breakthrough in the field of genetic hearing loss, demonstrating meaningful hearing gains in nearly all children assessed so far in the CHORD trial. While the therapy remains investigational and longer-term data are pending, the results highlight the potential of addressing the genetic root cause of deafness rather than simply amplifying sound.
For families affected by otoferlin-related hearing loss, the prospect of a one-time therapy that restores physiologic hearing represents a paradigm shift. As Regeneron moves toward potential regulatory submission, the gene-therapy space for hearing loss may be entering a new chapter.
Regeneron’s continued progress with DB-OTO highlights the company’s growing leadership in genetic medicine. By focusing on precision-targeted therapies, Regeneron is setting new standards in hearing restoration and demonstrating the transformative potential of gene-based treatments. As Regeneron advances toward FDA submission, the company’s success with DB-OTO could redefine how genetic hearing loss is treated and reinforce Regeneron’s position as a pioneer in the evolving field of auditory gene therapy.
