Regeneron Pharmaceuticals (Nasdaq: REGN) has received acceptance from the European Medicines Agency for a Marketing Authorization Application for Otarmeni (lunsotogene parvec), an adeno-associated virus-based gene therapy for biallelic OTOF variant-associated hearing loss. The MAA has been accepted under the EMA's Accelerated Assessment pathway, reserved for medicines considered to address major public health needs.
The MAA covers Otarmeni as a treatment for patients with hearing loss caused by biallelic variants in the OTOF gene, a rare condition affecting approximately 40 to 50 newborns annually in the EU. The EMA's decision to accept the application under Accelerated Assessment reflects the agency's classification of the therapy as addressing a major unmet medical need. Regeneron said regulatory submissions are also planned in Japan.
Otarmeni previously received Orphan Designation from the EMA. If the application results in approval, it would be the first gene therapy authorized for OTOF-related hearing loss in the EU. The therapy was approved in the US in April 2026 under accelerated approval, making the EMA filing the next step in Regeneron's international regulatory strategy for the asset.
The MAA is supported by data from the CHORD trial, an ongoing registrational Phase I/II multicenter, open-label study evaluating Otarmeni in infants, children, and adolescents with OTOF-related hearing loss. The trial enrolled 24 participants aged between 10 months and 16 years, who received a single intracochlear infusion of Otarmeni either unilaterally (n=10) or bilaterally (n=14).
An earlier data cut from CHORD involving 20 participants also supported the US FDA's accelerated approval of the therapy in April 2026. In that dataset, 80% of participants achieved hearing sensitivity at or below 70 decibels hearing level by pure tone audiometry at 24 weeks, meeting the trial's primary endpoint. Seventy percent met the key secondary endpoint of auditory brainstem response at or below 90 decibels at 24 weeks. With longer follow-up, 42% of participants achieved normal hearing thresholds at or below 25 decibels hearing level.
The science behind OTOF-related hearing loss
OTOF-related hearing loss, also referred to as DFNB9, is caused by biallelic loss-of-function variants in the OTOF gene, which encodes otoferlin. Otoferlin is a calcium-sensor protein essential for neurotransmitter release at the ribbon synapse of inner hair cells. Without functional otoferlin, inner hair cells cannot signal to the auditory nerve, producing profound congenital deafness despite structurally intact outer hair cells. The preservation of outer hair cell function means otoacoustic emissions are often recordable in affected patients, distinguishing the condition mechanistically from most other forms of sensorineural hearing loss and classifying it within auditory neuropathy spectrum disorder.
Otarmeni is designed to address this deficit directly. The therapy uses a dual AAV serotype 1 vector system to deliver a functional copy of the OTOF gene to inner hair cells via a single intracochlear infusion administered under general anesthesia. The dual-vector approach is necessary because the OTOF coding sequence exceeds the packaging capacity of a single AAV vector. Expression of the transgene is restricted to inner hair cells through a proprietary Myo15 promoter, intended to limit off-target activity. The newly expressed otoferlin protein is designed to restore synaptic vesicle exocytosis and auditory signaling at the inner hair cell to auditory nerve junction.