TARRYTOWN, NEW YORK — Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Otarmeni™ (lunsotogene parvec-cwha), marking the first gene therapy approved for a genetic form of hearing loss.
The approval represents a significant milestone for a field that has been steadily advancing in recent years. As previously discussed in an earlier interview with Regeneron’s Auditory Global Program Head Dr. Jonathon Whitton, the company has been developing gene therapy approaches targeting otoferlin-related hearing loss (OTOF), a rare genetic condition that disrupts communication between inner ear sensory cells and the auditory nerve. That work, formerly known as DB-OTO, has now culminated in the FDA approval of Otarmeni.
The therapy is indicated for pediatric and adult patients with severe-to-profound sensorineural hearing loss associated with biallelic variants in the OTOF gene. Otarmeni is also the first and only in vivo gene therapy for this condition and will be made available at no cost to eligible patients in the United States.
The approval is based on results from the pivotal CHORD clinical trial, where 80% of participants achieved significant improvements in hearing sensitivity at 24 weeks. Among those followed longer, 42% achieved hearing levels within the normal range, including the ability to perceive whispers.
Otarmeni represents the first FDA-approved example of a gene therapy capable of restoring a neurosensory function to near-normal levels.
“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,” said A. Eliot Shearer, M.D., Ph.D., 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.
“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.”
“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 D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. “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 U.S. and serves to highlight our belief that the biopharmaceutical industry can be a genuine force for good in the world.”
OTOF-related hearing loss is an ultra-rare condition, affecting approximately 50 newborns per year in the United States. The condition results from mutations in the OTOF gene, which impair production of otoferlin—a protein essential for communication between inner ear sensory cells and the auditory nerve. While hearing devices can provide amplification, they do not restore natural hearing function.
“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. “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.”
Clinical Trial Results
The FDA approval is supported by data from the Phase 1/2 CHORD trial, which enrolled 20 participants aged 10 months to 16 years who received a single intracochlear infusion of Otarmeni.
- 80% (16 of 20) experienced hearing improvements based on pure tone audiometry (PTA), achieving thresholds of ≤70 dB HL at 24 weeks and meeting the trial’s primary endpoint; one additional participant reached this threshold by week 48. This level is considered a clinically meaningful benchmark, enabling functional hearing that typically does not require cochlear implantation.
- 70% (14 of 20) demonstrated an auditory brainstem response (ABR) at ≤90 dB at 24 weeks, meeting the trial’s key secondary endpoint. ABR provides an objective measure of hearing by recording electrical brainstem responses to sound.
- Among participants followed to 48 weeks, all prior responders maintained their improvements, and 42% (5 of 12) achieved hearing levels within the normal range (≤25 dB HL), including the ability to detect soft sounds such as whispers.
Access and Availability
Regeneron stated that Otarmeni will be provided at no cost to clinically eligible individuals in the U.S., though administration-related costs may still apply.
Regulatory Status
Otarmeni has received Orphan Drug, Rare Pediatric Disease, Fast Track, and RMAT designations from the FDA.
Additional Insights
For additional context on the development of this therapy, readers can revisit our April 2025 interview with Regeneron’s Auditory Global Program Head Dr. Jonathon Whitton, who discussed the scientific rationale behind targeting the OTOF gene, the challenges of delivering gene therapy to the inner ear, and the potential for these approaches to reshape treatment for genetic hearing loss.
About Otarmeni™ (lunsotogene parvec-cwha)
Otarmeni is an adeno-associated virus vector-based gene therapy indicated for the treatment of certain pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss caused by variants of the OTOF gene that produce non-functioning otoferlin protein. The treatment is 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.
IMPORTANT SAFETY INFORMATION: Before receiving OTARMENI, patients should consult their healthcare provider regarding vaccinations and surgical risks. Serious risks associated with the procedure may include vertigo, tinnitus, cerebrospinal fluid leak, facial weakness, meningitis, infection, and inner ear inflammation. The most common side effects include middle ear infection, nausea, vomiting, dizziness, and procedural pain. Patients are encouraged to report side effects to the FDA at www.fda.gov/medwatch or call 1-800-FDA-1088.
About the CHORD Trial
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 (<18 years of age) 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 PTA and 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 dB. ABR corroborates these behavioral responses, serving as an objective confirmation of hearing function, and is measured through recording electrical brainstem responses to sound emitted at different intensity levels measured in dBs. At baseline, all participants had profound hearing loss (behavioral PTA), and no electrophysiological (ABR) responses at maximum sound levels.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.
Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.
Source: Regeneron
