Gene therapy improves hearing in children with form of genetic deafness

Ten out of 11 children with profound deafness, enrolled in a gene therapy trial, showed notable improvements in their hearing after a year.

The gene therapy known as DB-OTO was given to 12 children with otoferlin-related hearing loss, aged between ten months and 16 years. The results were presented at a recent meeting of the Association for Research in Otolaryngology. Ten of the 11 children who were assessed post-treatment showed notable improvements in hearing. The findings follow earlier results from the CHORD clinical trial (see BioNews 1238) that demonstrated hearing restoration in two patients who had received the gene therapy.

'A year after treatment in one ear with DB-OTO, a child born profoundly deaf was able to enjoy music, engage in imaginative play, and participate in bedtime reading when the cochlear implant on their other ear was removed. 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,' said Professor Jay Rubinstein, from the University of Washington School of Medicine.

Mutations in the OTOF gene, which codes for the protein otoferlin, are ultra-rare and can lead to profound congenital hearing loss. Regeneron's gene therapy DB-OTO is a cell-selective, modified harmless virus bearing a working copy of the OTOF gene designed to replace the faulty copy of the gene. DB-OTO is delivered via a surgical procedure similar to a cochlear implantation.

After less than a year, the first patient to be dosed demonstrated improvements in formal speech perception tests, as the child was able to correctly identify words, such as mommy, cookies and airplane, at a conversational level without any visual cues. Furthermore, after six months, three out of five children who were assessed experienced improvements to 'nearly normal' or 'normal' hearing levels. However, one child did not show any improvement in hearing at this point.

'You can see the efficacy very early on,' Dr Christos Kyratsous, Regeneron's senior vice president and co-head of genetic medicines, told Fierce Biotech. 'We are actively talking to FDA and other agencies around the world to understand what the clinical data set [is] but also everything else that you need to put together for your package to eventually get a drug approved.'

The research team has found the surgery and the gene therapy to be well tolerated, and no serious side effects caused by DB-OTO have been observed in the patients. Nevertheless, five of 12 participants experienced transient side effects, including uncontrollable eye movements, nausea, dizziness and vomiting, which all resolved within six days of treatment.

It is worth noting that the safety and efficacy of DB-OTO for otoferlin-related hearing loss has not been evaluated by any regulatory authority, as it is still under clinical investigation.