Regeneron Nets Accelerated Approval From FDA for Otoferlin-Related Hearing Loss Gene Therapy Lunsotogene Parvec

The FDA has granted accelerated approval to Otarmeni (lunsotogene parvec-cwha), an adeno-associated virus (AAV) vector–based gene therapy, for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss associated with biallelic pathogenic variants in the OTOF gene.¹ Eligible patients must have preserved outer hair cell function and no prior cochlear implant in the affected ear.

Otarmeni is the first in vivo gene therapy approved for OTOF-related hearing loss, a condition estimated to affect approximately 50 newborns annually in the United States. Regeneron has announced that the therapy will be made available at no cost to clinically eligible patients in the United States, though out-of-pocket costs for the administration procedure may vary.

OTOF encodes otoferlin, a protein essential for synaptic vesicle fusion at the inner hair cell–auditory nerve synapse. Loss-of-function variants in OTOF result in auditory neuropathy spectrum disorder in which cochlear architecture is preserved but sound signal transmission to the auditory nerve is impaired. Otarmeni delivers a functional copy of the OTOF gene via intracochlear infusion under general anesthesia using a surgical approach comparable to cochlear implantation. A proprietary Myo15 cell-specific promoter is used to restrict transgene expression to the inner hair cells that normally produce otoferlin.

The accelerated approval was based on results from the pivotal, open-label, multicenter, phase 1/2 CHORD clinical trial (NCT05788536), in which 20 participants aged 10 months to 16 years with OTOF-related hearing loss received a single intracochlear dose of Otarmeni, administered either unilaterally (n=10) or bilaterally (n=10). The surrogate primary end point was improvement in hearing sensitivity as measured by average pure-tone audiometry (PTA) at week 24, with a threshold of ≤70 dB hearing level (HL)—a clinically meaningful threshold that typically does not necessitate cochlear implantation. Eighty percent of participants (16 of 20) met this threshold at 24 weeks, with 1 additional participant achieving the response by week 48. A key secondary end point, the presence of an auditory brainstem response (ABR) at ≤90 dB HL at 24 weeks, was achieved in 70% of participants (14 of 20), providing objective electrophysiological corroboration of the behavioral hearing assessments. Among the 12 participants with at least 48 weeks of follow-up, all prior responders maintained their hearing response, and 42% (5 of 12) achieved hearing levels in the normal range (≤25 dB HL), including the ability to detect whispered speech.

“The FDA approval of Otarmeni signals a new era in the treatment of genetic forms of hearing loss, where reinstating 24/7 natural hearing is now possible,” A. Eliot Shearer, MD, PhD, an otolaryngologist in the department of Otolaryngology and Communication Enhancement at Boston Children’s Hospital, Associate Professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School and a CHORD trial investigator, said in a statement.¹ “In the pivotal trial, the one-time gene therapy demonstrated rapid, meaningful and consistent hearing responses, with most children achieving remarkable hearing improvements. I’ve witnessed firsthand my trial participant responding to their mother’s voice, dancing to music and interacting with the world, and these moments are now possible for more children born with this specific form of hearing loss.”

As accelerated approval was granted on the basis of hearing sensitivity as a surrogate endpoint, continued approval will be contingent on verification of clinical benefit in the confirmatory phase of the ongoing CHORD trial. The most common adverse reactions reported in the safety population (n=24), each occurring in at least 5% of participants, were otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus. Serious adverse events associated with the intracochlear surgical procedure—including vertigo, cerebrospinal fluid leak, meningitis, mastoiditis, and partial facial nerve paresis—were identified as risks in the prescribing information and require appropriate pre- and perioperative management.

“Otarmeni is a huge scientific leap and is representative of Regeneron’s approaches to continually push the boundaries of science to benefit humanity,” George D. Yancopoulos, MD, PhD, board cochair, president and chief scientific officer of Regeneron, added to the statement.¹ “This unprecedented breakthrough in gene therapy has already proven to be life-changing for many of the children in our clinical trial and their families. We are honored to be in the position to be the first company to ever offer such a gene therapy advance for free to those in the US and serves to highlight our belief that the biopharmaceutical industry can be a genuine force for good in the world.”

CGTLive® previously spoke to CHORD investigator Lawrence R. Lustig, MD, the chair of the Department of Otolaryngology—Head and Neck Surgery at Columbia University College of Physicians, about earlier data from CHORD that he presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD.² In the interview, Lustig also touched on how he expects early success with hearing loss gene therapy will impact the field of hearing loss treatment and spoke about overcoming the challenge of delivering the relatively large otoferlin gene with the dual AAV vector.

“This is going to be big for the field,” Lustig told CGTLive. “Now that we have a treatment for genetic deafness, our hope is that this will spur universal genetic testing in all kids with hearing loss, which will give us a much better overview of the genetic landscape of hearing loss in the world. Right now, we know there's a few genes that when they're mutated will lead to deafness, but there's many others for which it's not so clear.”

REFERENCES
1. Otarmeni (lunsotogene parvec-cwha) approved by FDA as first and only gene therapy for genetic hearing loss; Regeneron to provide otarmeni for free in the U.S. News release. Regeneron Pharmaceuticals, Inc. April 23, 2026. Accessed April 24, 2026. https://investor.regeneron.com/news-releases/news-release-details/db-oto-results-new-england-journal-medicine-showcase-dramatic
3. Lustig L, Bance M, Ishiyama A, et al. Intracochlear administration of DB-OTO gene therapy in pediatric patients with profound hearing loss due to otoferlin mutations: the CHORD phase 1/2 open-label trial. Presented at: ASGCT Annual Meeting 2024, May 7-10; Baltimore, Maryland. Abstract #10.