Gene therapy for OTOF deafness

Otoferlin is a protein that the sensory hair cells of the ear need to pass on sound signals at their synapses. Children who inherit two nonworking copies of its gene, OTOF, make none of it and are deaf from birth or before they learn to speak. The FDA puts OTOF variants at 2% to 8% of inherited non-syndromic cases. No medicine treated the cause, and these children usually received cochlear implants.

Early human results came from a single-centre trial registered in China. Between October 2022 and June 2023 it gave six children one injection of an AAV1 vector carrying human OTOF, placed in the cochlea through the round window. Five recovered some hearing, with average auditory brainstem response thresholds falling by 40 to 57 dB, and no child had a dose-limiting toxicity. The Lancet published the results in 2024.

Regeneron's product, DB-OTO, is a dual AAV1 gene therapy that delivers the human OTOF sequence under a promoter specific to hair cells. In its CHORD study, children with profound deafness (average thresholds above 90 dB) received an infusion of 7.2 × 10^12 vector genomes into one or both cochleas. At week 24, 9 of the 12 children reached an average pure-tone threshold of 70 dB or better, a level the investigators said generally avoids implantation. Six could hear soft speech without devices, and three had average normal hearing sensitivity. The New England Journal of Medicine published the report online on 12 October 2025.

The FDA granted Otarmeni (lunsotogene parvec-cwha) accelerated approval on 23 April 2026, 61 days after the filing, under the Commissioner's National Priority Voucher pilot program. The label covers children and adults with severe-to-profound or profound OTOF-related hearing loss who keep outer hair cell function and have no cochlear implant in the ear to be treated. The decision rested on a single-arm trial in 24 children aged 10 months to 16 years; 80% of the 20 who could be evaluated heard better. Middle ear infection, nausea, dizziness and procedural pain were common side effects. Continued approval may depend on evidence that the gains last and that speech development and quality of life improve.