The result comes from a phase 1/2 trial of the biotech’s experimental adeno-associated virus (AAV) gene therapy DB-OTO.
Opal Sandy, now aged 18 months, was born with profound deafness attributed to auditory neuropathy, a condition stemming from disrupted nerve impulses between the inner ear and the brain.
One of the youngest children in the world to receive a gene therapy for genetic deafness, she was treated at 11 months of age.
A second child in the CHORD trial, treated at age four, has also seen positive results after six weeks, according to data presented at the American Society of Gene and Cell Therapy (ASGCT) annual conference.
Professor Manohar Bance, an ear surgeon at Cambridge University Hospitals NHS Foundation Trust and the lead researcher for the trial, conveyed to the PA news agency that the findings surpassed his initial hopes and expectations, potentially indicating a breakthrough in treating patients with this form of hearing impairment.
“We have results from [Opal] which are very spectacular – so close to normal hearing restoration. So we do hope it could be a potential cure,” he said.
Regeneron's DB-OTO aims to address mutations found in the otoferlin gene, known as OTOF, responsible for encoding a substantial protein present in hair cells within the cochlea, which plays a crucial role in converting sound into neuronal signals.
In the ongoing study, patients receive a single intracochlear injection of DB-OTO in one ear and a cochlear implant in the other.
Following treatment, the children then take part in several hearing and brain tests, focusing on the tones needed for speech.
The trial’s secondary endpoints include hearing improvement, measured using auditory brainstem response (ABR) and behavioural audiometry with pure-tone audiometry (PTA).
“The opportunity of providing the full complexity and spectrum of sound in children born with profound genetic deafness is a phenomenon I did not expect to see in my lifetime,” said Lawrence Lustig, trial investigator and otolaryngologist at Columbia University.
“These impressive results showcase the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related deafness, and we are excited to see how this translates into an individual’s development, especially since early intervention is associated with better outcomes for speech development.
"With the DB-OTO CHORD trial now enrolling participants in sites across the U.S. and Europe, we’re part of the beginning of a new era of gene therapy research that looks to create treatment options that address the root cause of profound genetic deafness.”
At the start of the study, both pediatric patients showed no reaction to sounds delivered at maximum levels of 100 decibels or more, and there was no evidence of a signal reaching the hearing centres of the brain using electrophysiological auditory evoked response (ABR) testing.
However, at 24 weeks Opal observed improvement of her hearing to normal levels, with an average 80 decibels improvement from baseline.
The second child observed an average 16 decibels improvement in hearing response, compared to baseline, at six weeks.
In addition, the surgical procedure and the gene therapy were found to be well tolerated, with no treatment-related adverse events or serious adverse events.
According to Regeneron, the study is still recruiting participants across the US and Europe and aims to enrol approximately 22 children with otoferlin hearing loss aged 17 years and younger.
