The adeno-associated virus vector-based gene therapy is indicated for pediatric and adult patients with severe-to-profound hearing loss due to biallelic OTOF gene variants.
The US Food and Drug Administration (FDA) has granted accelerated approval for Otarmeni (lunsotogene parvec-cwha), a gene therapy for pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss associated with molecularly confirmed biallelic variants in the OTOF gene. The therapy, developed by Regeneron Pharmaceuticals, is indicated for patients with preserved outer hair cell function who have not had a prior cochlear implant in the same ear.
The accelerated approval is based on results from the pivotal CHORD trial, which demonstrated improvement of hearing sensitivity by average pure tone audiometry (PTA) at week 24. In the trial, 80% of participants achieved or surpassed a hearing level that met the primary endpoint. With longer follow-up, 42% of participants achieved normal hearing, including the ability to hear whispers. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory portion of the CHORD trial.
OTOF-related hearing loss is an ultra-rare condition where variants in the OTOF gene lead to a lack of functional otoferlin protein, which is necessary for communication between the inner ear’s sensory cells and the auditory nerve. Otarmeni is designed to deliver a working copy of the OTOF gene via a single intracochlear infusion.
“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,” says A. Eliot Shearer, MD, PhD, otolaryngologist in the department of Otolaryngology and Communication Enhancement at Boston Children’s Hospital, associate professor of otolaryngology-head and neck surgery at Harvard Medical School, and a CHORD trial investigator, in a release. “In the pivotal trial, the one-time gene therapy demonstrated rapid, meaningful and consistent hearing responses, with most children achieving remarkable hearing improvements.”
The surgical procedure to deliver Otarmeni is similar to cochlear implantation and is intended to be administered by a surgeon experienced in intracochlear surgery. The most common adverse reactions (≥5%) reported in the CHORD trial safety population included otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus.
Regeneron announced it will provide Otarmeni at no cost to clinically eligible individuals in the US. The company noted that this does not necessarily cover out-of-pocket costs for the administration of the therapy, and individuals should consult with their healthcare and insurance providers. Otarmeni also received Orphan Drug, Rare Pediatric Disease, and Fast Track designations from the FDA.
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