FDA Grants Accelerated Approval to Otarmeni, First and Only Gene Therapy for Genetic Hearing Loss

The FDA granted accelerated approval to lunsotogene parvec-cwha (Otarmeni, formerly DB-OTO; Regeneron Pharmaceuticals, Inc) for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency higher than 90 decibel hearing level [dB HL]) associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function, and no prior cochlear implant in the same ear.¹

With this action, Otarmeni has become the first gene therapy and second new molecular entity approved under the FDA Commissioner’s National Priority Voucher program, as well as the first and only in vivo gene therapy for OTOF-related hearing loss.¹

What Is Otarmeni?

Otarmeni is an adeno-associated virus vector–based gene therapy designed to restore durable, physiological hearing in individuals by delivering a functional copy of the OTOF gene via a modified, nonpathogenic virus, administered via cochlear infusion under general anesthesia. In this therapy, the newly introduced OTOF gene is under the control of a proprietary cell-specific Myo15 promoter intended to restrict expression to hair cells that normally express the otoferlin protein. The gene therapy’s administration method is similar to the procedure conducted for cochlear implantation, according to the manufacturer’s news release.¹

“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,” CHORD trial investigator A. Eliot Shearer, MD, PhD, otolaryngologist in the Department of Otolaryngology and Communication Enhancement at Boston Children’s Hospital, and associate professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School, said in the news release. “In the pivotal trial, the 1-time gene therapy demonstrated rapid, meaningful, and consistent hearing responses, with most children achieving remarkable hearing improvements.”¹

Clinical Data Bolstering Approval

According to the manufacturer’s news release, the approval is based on results from CHORD (NCT05788536),² an open-label, multicenter phase 1/2 trial evaluating the safety, tolerability, and efficacy of Otarmeni in 20 children and infants with biallelic hOTOF mutations. The ongoing trial is divided into 2 parts: Otarmeni is administered as a single intracochlear injection either unilaterally (in 1 ear, n = 10; part A) or bilaterally (in both ears, n = 10; part B), and for bilateral injections (part B), patients will receive Otarmeni in 1 surgical session.^1,2

The primary end points were incidence and severity of treatment-emergent adverse events (AEs) and achievement of a hearing sensitivity threshold of 70 or less dB assessed by average pure tone audiometry (PTA), which were assessed up to week 48. Secondary end points include auditory brainstem response to click, speech awareness threshold, and speech reception threshold, among others.²

The findings indicated that approximately 80% (n = 16) of Otarmeni-treated patients experienced hearing improvement, as assessed by PTA at a threshold of 70 dB HL or lower, at 24 weeks, achieving the trial’s primary end point. One additional participant was reported to have met this threshold by week 48, the news release noted. This threshold corresponds to a clinical standard that enables natural hearing and typically does not require cochlear implantation.¹

Further, approximately 70% (n = 14) of patients demonstrated an auditory brainstem response at 90 dB or lower at 24 weeks. For those followed for 48 weeks, all prior responders maintained a response to therapy, and approximately 42% of all participants (n = 5) achieved normal hearing that included whispers (≤ 25 dB HL).¹

The most common AEs (≥ 5%) in the safety population of CHORD (n = 24) associated with Otarmeni include otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus.¹

“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, said in the news release. “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.”

Future Considerations

The news release noted that continued approval for this indication may depend on the verification and description of clinical benefit in the confirmatory portion of the CHORD clinical trial.¹ Additionally, the approval’s clinical relevance is partially tied to the limitations of the current management of hearing loss. For example, hearing aids may amplify sound but do not correct defects in synaptic transmission, and cochlear implantation—while often beneficial to deafness or hearing loss related to OTOF—requires an implanted device and long-term hardware dependence.^3,4

“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,” Janet DesGeorges, executive director of Hands & Voices, said in the news release. “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.”¹

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 US. News release. Regeneron Pharmaceuticals. April 23, 2026. Accessed April 23, 2026. https://investor.regeneron.com/news-releases/news-release-details/otarmenitm-lunsotogene-parvec-cwha-approved-fda-first-and-only

2. A study of DB-OTO, an adeno-associated virus (AAV) based gene therapy, in children/​infants with hearing loss due to otoferlin mutations (CHORD). ClinicalTrials.gov. Updated February 23, 2026. Accessed April 23, 2026. https://clinicaltrials.gov/study/nct05788536

3. Shearer AE, Smith RJ. Massively parallel sequencing for genetic diagnosis of hearing loss: the new standard of care. Otolaryngol Head Neck Surg. 2015;153(2):175-182. doi:10.1177/0194599815591156

4. Delmaghani S, El-Amraoui A. Inner ear gene therapies take off: current promises and future challenges. J Clin Med. 2020;9(7):2309. doi:10.3390/jcm9072309