Two teams, one in China and one in the U.S., late last week announced positive results using gene therapy for profound genetic hearing loss due to mutations of the otoferlin gene. Such mutations cause only one to three percent of cases of hearing loss. But these developments represent a key step forward as there are currently no treatments for hearing loss except cochlear implants.
The team in China reported on several deaf children who were tested with a gene therapy. Four of five children regained their hearing in the treated ear. Yilai Shu, a surgeon and scientist at Fudan University in Shanghai, who is leading the work, presented these results at the meeting of the European Society for Gene and Cell Therapy in Brussels, according to a report in MIT Technology Review. Video footage accompanying the article shows a six-year-old trial participant chatting with her mother after removing her cochlear implant. The child has been deaf from birth.
Regeneron, meanwhile, announced preliminary, positive safety and efficacy results from the first patient (<2 years of age) dosed in the Phase I/II CHORD trial investigating its otoferlin gene therapy (DB-OTO) in children with profound genetic hearing loss. The trial is currently enrolling patients across sites in the U.S., United Kingdom, and Spain.
“… otoferlin, essentially turns off their auditory circuits,” said Professor Manohar Bance, MB, an ear surgeon and principal trial investigator at Cambridge University Hospitals’ NHS Foundation Trust in the United Kingdom.
He added that,“Cochlear implants are the current standard of care but are unable to replicate the full complexity and range of sound. With these very preliminary DB-OTO results, we now have encouraging evidence that this gene therapy may be able to help turn these auditory circuits back on. We look forward to following this child and others further to determine if DB-OTO gene therapy can restore clinically meaningful hearing as they are learning to interact with the world.”
In the trial, the child received an intracochlear injection of DB-OTO in one ear. At planned follow-ups, the child experienced improvements in auditory responses through week six compared to baseline, per auditory brainstem response (ABR) and behavioral (pure tone) audiometry. ABR, a clinically accepted physiologic measure of hearing sensitivity, is often absent in those with classic otoferlin-related hearing loss and was absent in both ears of the child at baseline. There were no concerning safety signals through week six following treatment.
Regeneron acquired the gene therapy as part of its recent $109 million purchase of Decibel Therapeutics. But Regeneron reports that DB-OTO is part of its growing pipeline of genetic medicines for hearing loss and other therapeutic areas that are being advanced by the company.
Congenital hearing loss (hearing loss present at birth) is a significant unmet medical need with no approved pharmacologic treatment options that affects approximately 1.7 out of every 1,000 children born in the U.S. While hearing loss caused by mutations of the otoferlin gene is ultra-rare, the majority of permanent, congenital hearing loss cases diagnosed in developed countries are sensorineural and result from a single gene defect, making them suitable targets for gene therapy.
