FDA approves Regeneron’s Otarmeni as first gene therapy for genetic hearing loss

The US FDA has approved Otarmeni (lunsotogene parvec-cwha), the first gene therapy for genetic hearing loss, granting Regeneron Pharmaceuticals accelerated approval for treatment of pediatric and adult patients with severe-to-profound sensorineural hearing loss caused by biallelic variants in the OTOF gene. The approval marks the first use of a dual adeno-associated virus (AAV) vector platform to reach regulatory clearance and the first disease-modifying treatment available for OTOF-related deafness.

The indication covers patients with hearing loss measuring greater than 90 dB HL at any frequency, with molecularly confirmed biallelic OTOF variants, preserved outer hair cell function, and no prior cochlear implant in the treated ear. Otarmeni and its administration kit constitute a one-time biologic-device combination product, delivered as a single surgical dose per ear into the cochlea via a syringe and catheter connected to an infusion pump. The therapy uses a dual AAV serotype 1 vector to deliver a functional copy of the OTOF gene to inner hair cells, restoring production of otoferlin, the calcium-sensitive protein required for synaptic vesicle exocytosis at the inner hair cell ribbon synapse. Without functional otoferlin, sound-evoked neurotransmission to spiral ganglion neurons is disrupted, producing congenital deafness that, prior to this approval, had no pharmacological intervention.

The FDA’s approval was based on data from the pivotal CHORD trial, in which 20 pediatric participants (aged 10 months to 16 years) received a single intracochlear dose, either unilaterally or bilaterally. At 24 weeks, 80% (16/20) achieved the primary endpoint of improved hearing based on pure tone audiometry (≤70 dB HL), with one additional responder by week 48, a level generally consistent with functional natural hearing without the need for cochlear implants. The key secondary endpoint was also met, with 70% (14/20) demonstrating auditory brainstem responses at ≤90 dB, confirming objective hearing improvement. Among those followed to 48 weeks, all responders maintained benefit, and 42% (5/12) achieved normal hearing levels, including the ability to hear whispers. The therapy was generally well tolerated, with the most common adverse events (≥5%) including otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus; administration requires a specialized intracochlear surgical procedure performed by trained surgeons.

The accelerated approval was issued 61 days after biologics license application filing, under the Commissioner’s National Priority Voucher pilot program, making Otarmeni the sixth product approved under that scheme and the first gene therapy among them. The FDA said the timeline is tied for the fastest BLA approval in modern agency history. Continued approval remains contingent on assessment of hearing improvement durability and verification of treatment effects on speech development and quality of life measures.

OTOF-related hearing loss accounts for an estimated 2% to 8% of inherited non-syndromic deafness cases. Genetic mutations broadly underlie approximately half of congenital hearing loss, and patients with two non-functional OTOF copies fail to produce otoferlin, disrupting auditory signaling from birth. Delayed diagnosis can narrow the window for intervention and contribute to lasting speech and language developmental delays, a clinical reality that has historically left cochlear implantation as the primary management strategy rather than a biological correction of the underlying deficit.

Otarmeni was originally developed as DB-OTO by Decibel Therapeutics, a company focused on auditory gene therapies. Regeneron acquired Decibel in September 2023 for an upfront payment of USD 109 million, building on a prior collaboration between the two companies. Regeneron has announced it will provide Otarmeni at no cost in the US, a pricing decision that removes one barrier to access for a therapy requiring surgical administration at specialist centers.

The approval arrives as the broader gene therapy field continues to refine AAV-based delivery platforms across neurological and sensory indications. The dual-vector design used in Otarmeni addresses a technical constraint specific to OTOF: the gene’s coding sequence exceeds the packaging capacity of a single AAV capsid, requiring the payload to be split across two vectors that reconstitute within the target cell. This approach had not previously supported an approved product, and its regulatory clearance establishes a precedent for other large-gene targets where single-vector delivery is not feasible.

Within hearing loss specifically, the competitive research landscape includes programs targeting other monogenic causes of deafness, though none has yet reached approval. The OTOF indication represents a defined molecular subset with relatively straightforward patient identification through genetic screening, a feature that supports both trial design and post-approval deployment. Whether the clinical infrastructure required for cochlear gene therapy delivery, which demands surgical precision and audiological follow-up, will constrain real-world uptake remains an open question the confirmatory trial data will need to address. Notably, Regeneron plans to provide Otarmeni at no cost to clinically eligible individuals in the US, not counting costs from healthcare providers administering the therapy.