Evidence builds behind Regeneron's deafness gene therapy

Ten out of 11 children with a form of congenital deafness who were treated with an experimental gene therapy developed by Regeneron have seen notable improvements in hearing, according to new data from the CHORD trial.

The update was reported at the Association for Research in Otolaryngology (ARO) this week and revealed that the first subject enrolled into the trial at 10 months of age, who had profound hearing loss from birth, now has near-normal hearing across key speech frequencies 72 weeks later and is making considerable progress in speech and development.

CHORD is a phase 1/2 in children with deafness due to variants of the otoferlin (OTOF) gene who are being treated with Regeneron's experimental adeno-associated virus (AAV) gene therapy DB-OTO in either one or both ears. OTOF is mutated in a small percentage of cases of sensorineural hearing loss (SNHL), the most common form of deafness affecting up to two per 1,000 newborns.

The first child – who was treated with DB-OTO in one ear – is now "able to enjoy music, engage in imaginative play and participate in bedtime reading when the cochlear implant on their other ear was removed," according to trial investigator Jay Rubinstein of the Bloedel Hearing Research Center at University of Washington School of Medicine,

"These seemingly small interactions are life-changing for these children, as well as their families, and these results continue to underscore the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related hearing loss," he added.

Among the other 12 participants aged 10 months to 16 years who have been treated with the gene therapy, nine have had it injected into one ear and three have received it in both.

At the ARO conference, data from 11 children with at least one post-treatment was presented with 10 showing improvements in hearing at various decibel hearing levels (dBHL), according to Regeneron.

Among five participants with 24-week assessments, three experienced improvements in average hearing thresholds to "nearly normal" hearing levels, while one subject saw no change in their hearing from baseline.

Regeneron – which acquired DB-OTO as part of its $109 million acquisition of Decibel Therapeutics in 2023 – is one of a handful of biopharma companies working on gene therapies for this type of deafness, along with French biotech Sensorion and Akouos, which was bought by Eli Lilly for $487 million upfront in 2022.

Sensorion is running the phase 1/2 Audiogene study of its candidate SENS-501, which recently cleared a safety assessment by its data monitoring committee on three children with otoferlin-related deafness aged between six and 31 months at the time of treatment. Another three subjects, who will receive a higher dose, are now due to be enrolled in the first half of this year.

Akouos and Lilly, meanwhile, said at last year's ARO conference that their AK-TOF improved hearing in a single 11-year-old subject in the phase 1/2 AK-OTOF-101 trial.

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