Imagine hearing your mother's voice for the first time.
For children born with otoferlin-related deafness — a form of profound genetic hearing loss caused by a mutation in a single gene — that moment has never been possible. No hearing aid helps. No technology bridges the gap. The inner ear simply cannot convert sound into the electrical signals the brain needs to make sense of the world.
Until now.
Results from the Phase 1/2 CHORD clinical trial of Regeneron's DB-OTO gene therapy, published in The New England Journal of Medicine, have shown something extraordinary: 11 out of 12 children treated with a single injection experienced clinically meaningful hearing improvements. Three of those children achieved completely normal hearing levels.
One child, who had never heard speech before, can now identify one- and two-syllable words without visual cues — and respond to conversation in a noisy room.
The science behind this achievement is elegant. The otoferlin gene (OTOF) provides instructions for making a protein critical to the hair cells of the inner ear. Without it, those cells cannot release the chemical signals that create sound perception. DB-OTO uses a dual adeno-associated virus (AAV) vector to deliver a functioning copy of the OTOF gene directly to the inner ear hair cells — essentially giving them the instruction manual they were born without.
The results came fast. Most children began showing hearing improvements within weeks of the single injection. By week 24, nine participants had achieved hearing thresholds that typically allow for natural acoustic hearing without cochlear implantation. In participants followed for 36 weeks or more, hearing gains remained stable or continued to improve — in some cases, up to 72 weeks of follow-up.
No therapy-related serious adverse events were reported. The procedure was well tolerated.
Regeneron has filed for FDA review. The agency has already granted DB-OTO Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations — every accelerated pathway available for a treatment this promising.
Otoferlin-related deafness affects a relatively small number of children, but the principle it demonstrates reaches far beyond them. If a single injection can restore hearing to a child who was born without it, the template exists for treating many other forms of genetic hearing loss — conditions that affect hundreds of millions of people worldwide.
For the families in the CHORD trial, that larger picture may feel distant. What they're living with is something more immediate and more beautiful: a child who can now hear them say 'I love you.'
And can hear them say it back. 👂