FDA Approves Regeneron’s Gene Therapy for Hearing Loss

Rare Daily Staff

The U.S. Food and Drug Administration has granted accelerated approval to Regeneron’s Otarmeni, the first and only gene therapy for a form of genetic hearing loss.

The company said it will provide the treatment free of charge to eligible patients in the United States. Otarmeni is the first gene therapy and the second new molecular entity approved under the FDA Commissioner’s National Priority Voucher program, which seeks to accelerate development in areas of high unmet need.

The one‑time therapy is approved to treat pediatric and adult patients with severe‑to‑profound and profound sensorineural hearing loss related to mutations in the OTOF gene, a rare condition that affects about 50 newborns each year in the United States. The approval marks the first FDA approval of a gene therapy restoring a neurosensory function to normal levels in some patients.

OTOF‑related hearing loss is considered an ultra‑rare condition in which all major structures of the ear are intact, but variants in the OTOF gene prevent production of functional otoferlin, a protein that enables communication between inner ear sensory cells and the auditory nerve. Historically, this type of genetic hearing loss has been considered permanent and managed with lifelong use of hearing aids or cochlear implants, devices that can improve access to sound but do not restore the full spectrum of hearing.

Otarmeni, formerly known as DB‑OTO, is an adeno‑associated virus vector‑based gene therapy designed to deliver a working copy of the OTOF gene directly into the cochlea, the spiral‑shaped structure of the inner ear. Patients receive the therapy as a single intracochlear infusion under general anesthesia in a procedure similar to cochlear implantation. The introduced gene is controlled by a cell‑specific Myo15 promoter, which is intended to restrict expression to the hair cells that normally produce the otoferlin protein needed to transmit sound signals to the auditory nerve.

Otarmeni has received Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the FDA, and Orphan Drug Designation from the European Medicines Agency.

The CHORD trial is continuing to enroll infants, children, and adolescents under 18 years of age at sites in the United States, the United Kingdom, Spain, Germany, and Japan to further evaluate the safety, tolerability, and durability of hearing improvements with Otarmeni.

The FDA’s decision is based on results from the ongoing CHORD trial, a phase 1/2 multicenter, open‑label study that enrolled 20 children and adolescents ages 10 months to 16 years with OTOF‑related hearing loss. Participants received a single dose of Otarmeni either in one ear (10 patients) or both ears (10 patients). At 24 weeks, 16 of 20 participants—80 percent—met the trial’s primary endpoint, reaching or surpassing a hearing threshold of 70 decibel hearing level or better on pure‑tone audiometry, a standard measure of hearing sensitivity. That level typically allows for natural hearing and usually does not require cochlear implantation.

A key secondary endpoint showed that 14 of 20 participants—70 percent—demonstrated an auditory brainstem response at 90 decibels or less at 24 weeks, providing objective confirmation of improved hearing function. For the 12 participants who had been followed for 48 weeks, all responders maintained their hearing gains, and five of 12, or 42 percent, achieved normal hearing, including the ability to hear whispers at 25 decibel hearing level or less.

“Otarmeni is a huge scientific leap and is representative of Regeneron’s approaches to continually push the boundaries of science to benefit humanity,” said George Yancopoulos, Regeneron’s board co‑chair, president, and chief scientific officer. He said the breakthrough has already been “life‑changing” for many children in the clinical trial and their families and called the decision to offer the therapy free in the United States an example of how the biopharmaceutical industry “can be a genuine force for good in the world.”