In the United States, a decision by the US Food and Drug Administration changes the situation for a small proportion of children born deaf. The federal agency has just authorized for the first time a gene therapy for genetic deafnessintended for an ultra-rare form of profound sensorineural deafness. Two to three children out of 1,000 births have a hearing problem, and more than half of this early deafness is linked to genetic mutations.
The FDA authorizes Otarmeni: this new miracle treatment for certain deaf children
This green light aims Otarmeni (or lunsotogene parvec-cwha), a treatment developed by Regeneron Pharmaceuticals for patients whose deafness is linked to the OTOF gene. This single injection therapy into the cochlea provides a functional copy of the gene, to restore the production of otoferlin, a key protein in the transmission of sound to the brain. In the CHORD trial, 80% of 20 children treated saw significant hearing improvement within months, and the company says Otarmeni will be provided free of charge to eligible patients in the United States.
How Otarmeni acts on deafness linked to the OTOF gene
In this form of deafness, the ear appears normal, but variants in the OTOF gene prevent the production of otoferlin. Without this protein, cells in the inner ear no longer transmit sound signals to the auditory nerve. Children often pass neonatal screening without warning, and deafness is only identified around 2 or 3 years of age, when language is not developing. It is estimated that around 50 infants per year are born with OTOF-related hearing loss in the United States, and that around 20,000 people are affected in the United Kingdom, Germany, France, Spain and Italy.
In the CHORD trial, 20 children and adolescents aged 10 months to 16 years received Otarmeni by intracochlear injection, in one or both ears. At the end of 24 weeks, 80% had reached a hearing threshold less than or equal to 70 decibels, a level compatible with conversation without a cochlear implant. Among those followed for 48 weeks, 42% had so-called normal hearing, including whispering, and the responders maintained their benefit.
We told you the story of one of the first children included in this study: little Opal.
Further OTOF Gene Trials Confirm Potential of Gene Therapy
Other teams are working on gene therapies to correct this disorder. In China, ten patients with profound OTOF-related hearing loss, aged 1 to 24 years, received an injection of genetic material into the cochlea; their average hearing threshold increased from around 106 decibels to 52 after six months, representing the transition from profound deafness to sufficient hearing for many everyday sounds. The youngest have progressed the most, especially between 5 and 8 years old, a key period for language. For some children, gene therapy could avoid a cochlear implant. In the United States, other teams are involved with other Biotech companies.
What are the prospects for French families facing Otarmeni?
For the moment, Otarmeni is only offered in the United States, in a few specialized centers, even if the European Medicines Agency has already granted orphan drug status. In France, the challenge will be to quickly direct deaf children towards a genetic assessment in order to identify those whose deafness is linked to OTOF.