FDA Approves Regeneron's Otarmeni, First US Gene Therapy for Genetic Hearing Loss

The FDA on April 23 granted accelerated approval to Regeneron's Otarmeni (lunsotogene parvec-cwha), a one-time gene therapy for children and adults with severe-to-profound or profound hearing loss caused by variants in both copies of the OTOF gene, the agency announced. The FDA said no disease-modifying treatment previously existed for OTOF-related deafness.

The OTOF gene carries the instructions for otoferlin, a protein needed to pass sound signals from the inner ear's hair cells to the auditory nerve, CGTLive reported. The FDA said variants in OTOF account for 2% to 8% of inherited, non-syndromic hearing loss cases. The therapy is for patients with preserved outer hair cell function and no prior cochlear implant in the same ear.

How it works and the trial data

Otarmeni is a biologic-device combination product. It uses two adeno-associated virus serotype 1 (AAV1) vectors to deliver a working copy of the OTOF gene to inner hair cells, and it is infused surgically into the cochlea, one dose per ear, through a syringe and catheter connected to an infusion pump, the FDA said. The agency called it the first-ever dual AAV vector-based gene therapy.

The approval was based on the ongoing Phase 1/2 CHORD trial (NCT05788536), a single-arm study compared with the natural history of untreated hearing loss. It treated 24 patients aged 10 months to 16 years. Of 20 patients evaluable for efficacy, 80% had improved hearing, according to the FDA.

CGTLive reported, citing Regeneron, that the surrogate primary endpoint was average pure-tone audiometry of 70 dB hearing level or better at week 24, which 16 of the 20 participants reached; one more responded by week 48. Fourteen of 20 showed an auditory brainstem response at 90 dB or below at 24 weeks. Among 12 participants followed for at least 48 weeks, all earlier responders kept their response and five reached hearing levels in the normal range, the publication said.

"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 of Boston Children's Hospital, a CHORD investigator, in Regeneron's statement as quoted by CGTLive.

Safety, review and access

Common side effects included middle ear infection, nausea, dizziness and procedural pain, the FDA said, and providers should monitor for surgical complications. CGTLive reported that the prescribing information identifies serious adverse events associated with the surgical procedure, including vertigo, cerebrospinal fluid leak, meningitis, mastoiditis and partial facial nerve paresis, as risks.

The FDA said the approval was issued 61 days after the biologics license application was filed and was the sixth approval, and first gene therapy, under the Commissioner's National Priority Voucher pilot. The application also had orphan drug, rare pediatric disease, fast track and regenerative medicine advanced therapy designations. Continued approval may depend on assessing how long hearing improvement lasts and verifying effects on speech development and quality of life, the agency said.

Regeneron said it will provide Otarmeni at no cost to clinically eligible patients in the US, though out-of-pocket costs for the administration procedure may vary, according to CGTLive.