Health and Medicine
PUBLISHED
The US Food and Drug Administration (FDA) has just approved the first-ever gene therapy for a form of inherited hearing loss. The one-time treatment targets a gene that’s responsible for 2-8 percent of inherited deafness cases, and the approval comes after a clinical trial reported improvements in 80 percent of treated patients.
The rest of this article is behind a paywall. Please sign in or subscribe to access the full content.“Today’s approval is a significant milestone in the treatment of genetic hearing loss,” said FDA Commissioner Marty Makary in a statement.
Congenital hearing loss can be traced back to a genetic mutation in about half of cases, and the OTOF gene is responsible for a small portion of those – about 50 newborns per year in the US. The gene codes for a protein called otoferlin that plays an essential role in carrying sound signals from the inner ear to the brain.
A range of mutations in this gene have been associated with hearing loss. Gene therapy approaches seek to replace the mutated gene with a functioning copy in the hopes it will restore some hearing. One such approach was demonstrated in 2024 – the then 11-year-old patient was able to hear sounds for the first time in his life after successful treatment in one ear.
The treatment approved by the FDA is called Otarmeni and was developed by Regeneron Pharmaceuticals, a biotech company headquartered in New York. It’s unique among other approved gene therapies in that it uses two viral “vectors” to carry the target gene.
In gene therapy, a vector is the way in which the therapeutic genetic material is transported into the patient’s cells. The adeno-associated viruses (AAVs) that do this in Otarmeni aren’t harmful – they’re basically just transport capsules – and it can be necessary to use two when the gene of interest has a particularly long sequence and won’t fit inside a single vector.
Otarmeni is administered once into each ear and delivers the working copy of the OTOF gene directly to the hair cells of the inner ear. It’s being made available free of charge to patients in the US with severe-to-profound and profound hearing loss and no prior history of a cochlear implant.
The treatment is being validated in an ongoing trial, and it was approved under an accelerated review by the FDA based on initial results from 20 patients aged 10 months to 16 years who received the treatment in one or both ears.
By week 24 after treatment, 80 percent of them experienced hearing improvements and 70 percent saw an auditory brainstem response at a threshold of ≤90 decibels. Twelve participants were followed for up to 48 weeks – among them, five had achieved “normal hearing that included whispers.”
“In the pivotal trial, the one-time gene therapy demonstrated rapid, meaningful and consistent hearing responses, with most children achieving remarkable hearing improvements,” said trial investigator and otolaryngologist A. Eliot Shearer in a statement.
“I’ve witnessed firsthand my trial participant responding to their mother’s voice, dancing to music and interacting with the world, and these moments are now possible for more children born with this specific form of hearing loss.”
There were some side effects reported, such as middle ear infections and dizziness, but the treatment was found to be safe overall.
Otarmeni promises a much better result for some patients than has been possible with the current standard treatment – using sound amplification devices.
“Connection and communication are at the heart of how we experience the world – whether that happens through listening and spoken language, sign language, the use of technology, or a combination of approaches,” said Janet DesGeorges, Executive Director of nonprofit Hands & Voices.
“Families deserve access to balanced information and a range of options when navigating genetic hearing loss. As new treatments and innovations emerge, families can assess available options and choose the approach best suited to their unique circumstances.”
