FDA approves first gene therapy for genetic hearing loss

The US Food and Drug Administration (FDA) has approved lunsotogene parvec-cwha (Otarmeni), the first gene therapy for genetic hearing loss caused by biallelic variants in the OTOF gene, marking a milestone in the treatment of an ultra-rare condition that affects approximately 50 newborns per year in the United States.

The approval, announced April 23, 2026, by Regeneron Pharmaceuticals, represents the first FDA approval for a gene therapy to restore a neurosensory function to normal levels, according to the company.

"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, MD, PhD, an otolaryngologist at Boston Children's Hospital, associate professor at Harvard Medical School, 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."¹

Clinical Relevance and Regulatory Background

Lunsotogene parvec-cwha received accelerated approval based on the ongoing Phase 1/2 CHORD trial, an open-label, multicenter study evaluating the safety, tolerability, and efficacy of the adeno-associated virus (AAV) vector-based gene therapy delivered via intracochlear infusion. The trial enrolled 20 participants aged 10 months to 16 years with profound sensorineural hearing loss and molecularly confirmed biallelic OTOF variants. All participants had no measurable auditory brainstem response (ABR) at baseline.¹

Among the 20 treated participants, 80% (16 of 20) met the primary endpoint, achieving hearing sensitivity of 70 dB hearing level (HL) or better on pure tone audiometry at 24 weeks, which the release points out is a threshold generally considered sufficient for natural hearing without cochlear implantation. An additional participant reached this threshold by week 48.

On the key secondary endpoint, 70% (14 of 20) demonstrated an ABR at 90 dB or better at 24 weeks, providing objective electrophysiological confirmation of restored auditory function. Among participants followed to 48 weeks, all prior responders maintained their response, and 42% (5 of 12) achieved normal hearing, including the ability to detect whispers at 25 dB HL or better.¹

The most common adverse reactions reported in the safety population (n = 24) included otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus. Serious risks associated with the required intracochlear surgical procedure include vertigo, cerebrospinal fluid leak, partial facial paralysis, meningitis, and mastoiditis.¹

Understanding OTOF-Related Hearing Loss

OTOF-related hearing loss results from biallelic loss-of-function variants in the OTOF gene, which encodes otoferlin, a protein essential for synaptic vesicle fusion at inner hair cell ribbon synapses and thus critical for signal transmission between the cochlea and the auditory nerve.²

Although cochlear structures remain intact, the absence of functional otoferlin renders conventional hearing aids largely ineffective; cochlear implantation has been the primary management strategy. Otarmeni is designed to deliver a functional copy of the OTOF gene using a dual-AAV vector system under a proprietary Myo15 promoter intended to restrict expression to cochlear hair cells.¹

Lunsotogene parvec-cwha: Next Steps

The approval carries notable caveats. Lunsotogene parvec-cwha was granted accelerated approval based on the surrogate endpoint of hearing sensitivity improvement by average pure tone audiometry at week 24 and continued approval may be contingent upon verification of clinical benefit in the confirmatory portion of the CHORD trial, which remains ongoing across sites in the United States, United Kingdom, Spain, Germany, and Japan.

The therapy is not recommended for patients in whom preoperative imaging demonstrates infeasible inner ear access, including those with abnormal mastoid pneumatization or significant anatomic variations. Additionally, the therapy is contraindicated in patients with prior cochlear implantation in the same ear.¹

In their approval announcement, Regeneron pointed out it will provide lunsotogene parvec-cwha at no cost to clinically eligible individuals in the US. However, the company noted that out-of-pocket costs related to the surgical administration procedure may still apply.

The drug received Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the FDA, and the European Medicines Agency has granted Orphan Drug Designation with regulatory submissions planned in additional markets.¹

References

1. Regeneron Pharmaceuticals, Inc. Otarmeni (lunsotogene parvec-cwha) approved by FDA as first and only gene therapy for genetic hearing loss. Press release. April 23, 2026. Accessed April 23, 2026. https://investor.regeneron.com/news-releases/news-release-details/otarmenitm-lunsotogene-parvec-cwha-approved-fda-first-and-only
2. Roux I, Safieddine S, Bhatt DK, et al. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell. 2006;127(2):277-289.
3. US Food and Drug Administration. Accelerated approval program. Updated 2024. Accessed April 23, 2026. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program