Regeneron Pharmaceuticals, Inc. announced the European Medicines Agency (EMA) has accepted for review under Accelerated Assessment the Marketing Authorization Application (MAA) for Otarmeni (lunsotogene parvec), an in vivo adeno-associated virus vector-based gene therapy for the treatment of biallelic OTOF variant-associated hearing loss. Otarmeni, formerly known as DB-OTO, previously received Orphan Designation from the EMA. If approved, Otarmeni will be the first gene therapy for OTOF-related hearing loss in the European Union (EU).

The MAA is supported by data from the pivotal CHORD clinical trial, in which 24 participants (aged between 10 months to 16 years) received a single dose of Otarmeni via intracochlear infusion, either unilaterally (in one ear; n=10) or bilaterally (in both ears; n=14). An earlier cut of results from the CHORD trial (n=20) also supported the U.S. Food and Drug Administration?s recent accelerated approval of Otarmeni in April 2026. Regulatory submissions are planned in additional markets, including Japan.

OTOF-related hearing loss is an ultra-rare condition, affecting approximately 46 newborn children per year in the EU. Though all structures within the ear are intact, variants in the OTOF gene cause a lack of a functional otoferlin protein, which is critical for communication between the sensory cells of the inner ear and the auditory nerve. Historically, genetic OTOF-related hearing loss was considered permanent and managed with life-long use of devices.

While these devices can amplify sound to improve hearing for individuals with a range of hearing loss, they do not currently restore the full spectrum of sound. Otarmeni is approved in the U.S. Outside of the U.S., the safety and efficacy of Otarmeni have not been fully evaluated. The CHORD trial is an ongoing, registrational Phase 1/2 multicenter, open-label trial to evaluate the safety, tolerability and efficacy of Otarmeni in infants, children and adolescents with OTOF-related hearing loss.

The trial is currently enrolling children and adults across sites in the U.S., United Kingdom, Spain, Germany and Japan. CHORD is being conducted in two parts. In the initial dose-escalation cohort (Part A), participants receive a single intracochlear infusion of Otarmeni in one ear.

In the expansion cohort (Part B), participants receive Otarmeni in both ears at the selected dose from Part A. Hearing improvements were assessed by average pure tone audiometry (PTA) and auditory brainstem response (ABR). PTA is the gold standard measurement of hearing sensitivity and is measured through behavioral responses to sound (e.g., turning head towards sound) that is emitted at different intensity levels and measured in decibels (dB). ABR complements these behavioral responses, serving as an objective measure of synchronized neural response, to sound.

At baseline, all participants had profound hearing loss (behavioral PTA), and no electrophysiological (ABR) responses at maximum sound levels. Otarmeni is an in vivo dual adeno-associated virus serotype 1 (AAV1) vector-based gene therapy designed to restore durable, physiological hearing to individuals by delivering a working copy of the OTOF gene through a modified, non-pathogenic virus that is delivered via an infusion into the cochlea under general anesthesia (similar to the procedure used for cochlear implantation). In this gene therapy, the newly introduced OTOF gene is under the control of a proprietary cell-specific Myo15 promoter, which is intended to restrict expression only to hair cells that normally express the otoferlin protein.

Otarmeni is currently approved in the U.S. for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency >90 decibel hearing level [dB HL]) associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function, and no prior cochlear implant in the same ear. Before receiving OTARMENI: it is recommended to receive age-appropriate vaccinations, at least 1 month before the first corticosteroid dose and at least 1 month after the last corticosteroid dose. The following serious side effects may occur with the surgery required to administer OTARMENI: Vertigo, ringing in ear(s), cerebral spinal fluid leak, partial facial paralysis or weakness, change in taste, meningitis, wound infection, serious infection of the bone behind the ear (mastoiditis), numbness around the ear, blood or fluid collection at surgical site, and inflammation of the inner ear.

The most common side effects that may occur with OTARMENI include middle ear infection, vomiting, nausea, dizziness, procedural pain, walking disturbance, and rapid involuntary eye movements. Other clinically significant side effects, each occurring in 1 person in the clinical study, included temporary balance disorder, abnormal otoacoustic emissions, and wound separation. Because small quantities of OTARMENI may be present in bodily fluids/waste, any materials that may be contaminated should be placed in a sealable bag and disposed of into regular trash for the first two weeks following administration of OTARMENI.

Practice proper hand hygiene, such as hand washing, when coming into direct contact with bodily fluids/waste.