FDA approves Otarmeni™ gene therapy for genetic deafness
The US Food and Drug Administration (FDA; MD, USA) has granted accelerated approval to Otarmeni™, a gene therapy indicated for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural OTOF-related hearing loss.
Otarmeni, formerly known as DB-OTO, is the first and only in vivo gene therapy designed to address OTOF-related hearing loss. Variants in the OTOF gene result in a lack of functional otoferlin protein, which is essential for communication between the sensory cells of the inner ear and the auditory nerve. Unlike hearing aids or cochlear implants that amplify sound but do not restore the full spectrum of hearing, Otarmeni, developed by Regeneron Pharmaceuticals (NY, USA), aims to restore durable and physiological hearing by addressing the root cause of the condition.
This innovative therapy utilizes an adeno-associated virus vector to deliver a functional copy of the OTOF gene. The gene is introduced into the cochlea via an infusion under general anesthesia, using a modified, non-pathogenic virus. A proprietary cell-specific Myo15 promoter ensures that the gene is expressed exclusively in hair cells that naturally produce otoferlin protein.
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A new international study demonstrated the success of a gene therapy, AAV1-hOTOF, for treating autosomal recessive deafness 9.
Otarmeni is currently being evaluated in the ongoing Phase I/II CHORD trial, which is assessing its safety, tolerability and efficacy in infants, children and adolescents with OTOF-related hearing loss. The therapy received FDA accelerated approval based on improvements in hearing sensitivity, as measured by pure tone audiometry (PTA) at 24 weeks.
“The FDA approval of Otarmeni signals a new era in the treatment of genetic forms of hearing loss, where reinstating 24/7 natural hearing is now possible,” said A. Eliot Shearer, otolaryngologist in the department of Otolaryngology and Communication Enhancement at Boston Children’s Hospital (MA, USA), Associate Professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School (MA, USA) and a CHORD trial investigator. “In the pivotal trial, the one-time gene therapy demonstrated rapid, meaningful and consistent hearing responses, with most children achieving remarkable hearing improvements. 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.”
Key findings from the pivotal CHORD trial, which included 20 participants aged 10 months to 16 years, are as follows:
- Primary endpoint
80% (16 of 20 participants) achieved hearing improvements with PTA thresholds of ≤70 dB HL at 24 weeks, meeting the trial’s primary endpoint. One additional participant reached this threshold by week 48. This level of hearing typically enables natural hearing without the need for cochlear implants.
- Secondary endpoint
70% (14 of 20 participants) demonstrated auditory brainstem response (ABR) thresholds of ≤90 dB at 24 weeks, confirming hearing function through objective brainstem signal measurements.
- Long-term outcomes
Among participants followed to 48 weeks, all prior responders maintained their response, and 42% (5 of 12 participants) achieved normal hearing, including the ability to hear whispers (≤25 dB HL).
“Otarmeni is a huge scientific leap and is representative of Regeneron’s approaches to continually push the boundaries of science to benefit humanity,” said George D. Yancopoulos, Board Co-Chair, President and Chief Scientific Officer of Regeneron.
Regeneron has committed to providing Otarmeni at no cost to clinically eligible individuals in the United States.
“This unprecedented breakthrough in gene therapy has already proven to be life-changing for many of the children in our clinical trial and their families. We are honored to be in the position to be the first company to ever offer such a gene therapy advance for free to those in the US and serves to highlight our belief that the biopharmaceutical industry can be a genuine force for good in the world,” elaborated Yancopoulos.
More on Otarmeni
Breakthrough in gene therapy for genetic deafness
Results from the ongoing Phase I/II CHORD trial for the investigational gene therapy DB-OTO have detailed improvements in the hearing of two children, both born with genetic deafness.
Positive update on hearing loss gene therapy trial
At the Research in Otolaryngology’s 48th Annual MidWinter Meeting (22–26 February 2025; Orlando, FL), Regeneron Pharmaceuticals provided an update on the Phase I/II CHORD trial for DB-OTO.
Update on gene therapy trial for genetic deafness
Regeneron Pharmaceuticals has provided updated data from the pivotal CHORD trial assessing their investigational gene therapy DB-OTO.
