FDA approves the first gene therapy for genetic hearing loss

The FDA has granted an accelerated approval for Otarmeni (lunsotogene parvec-cwha), the first gene therapy to treat patients with biallelic variants in the OTOF gene. The gene therapy will be made available to eligible patients at no cost, according to a news release from Regeneron, the therapy’s developer.

OTOF gene hearing loss, also known as autosomal recessive deafness 9, is an ultra-rare condition, affecting about 50 newborns per year in the United States. Although 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 lifelong use of devices.

Otarmeni is an adeno-associated virus vector-based gene therapy indicated for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency >90 decibel hearing level) associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function, and no prior cochlear implant in the same ear.

“Connection and communication are at the heart of how we experience the world—whether that happens through listening and spoken language, sign language, the use of technology, or a combination of approaches,” said Janet DesGeorges, executive director of Hands & Voices, a parent organization for those with deaf children. “Families deserve access to balanced information and a range of options when navigating genetic hearing loss. As new treatments and innovations emerge, families can assess available options and choose the approach best suited to their unique circumstances.”

Otarmeni, formerly known as DB-OTO, is the first in vivo gene therapy for OTOF-related hearing loss and the second new molecular entity approved under the FDA’s National Priority Voucher program, a pilot program to shorten the review process from what normally takes 10 months to 12 months to between 1 month and 2 months. This program uses a collaborative tumor board-style review process to accelerate approvals.

Regeneron expects Otarmeni to be available within weeks and is actively working with treatment centers to ensure their readiness to receive and administer the gene therapy. Regeneron will provide Otarmeni at no cost to eligible patients, but the manufacturer indicated patients’ out-of-pocket costs will likely include the cost for administration.

“We are providing Otarmeni for free in the U.S. to remove financial barriers and facilitate equitable access to Otarmeni,” a Regeneron spokesperson told Managed Healthcare Executive. “We want to help ensure clinically appropriate patients of this ultra-rare condition can access Otarmeni regardless of their insurance status or ability to pay.”

The approval is based on results from the pivotal CHORD trial, in which 20 participants (aged 10 months to 16 years) received a single dose of Otarmeni via intracochlear infusion, either unilaterally (10 patients received the therapy in one ear) or bilaterally (10 received the therapy in both ears).

In the trial, 16 of the 20 patients, or 80%, experienced hearing improvements per pure tone audiometry assessments at a threshold of ≤70 dB HL at 24 weeks, achieving the trial’s primary endpoint; one additional patient achieved this threshold by week 48. This threshold corresponds to a clinical standard that enables natural hearing and typically does not require cochlear implantation.

Additionally, 14 of 20, or 70%, demonstrated an auditory brainstem response (ABR) at ≤90 decibels at 24 weeks, achieving the trial’s key secondary endpoint. ABR is an objective confirmation of hearing function, measured by recording electrical brainstem signals in response to sound.

At week 48, patients who had responded maintained that response, and five patients achieved normal hearing, including hearing whispers.

The most common adverse reactions in the safety population of CHORD, which included 24 patients, include otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus.