Approved Thursday via the FDA’s Commissioner’s National Priority Voucher program, Otarmeni is the first gene therapy for hearing loss—and the first treatment to target an underlying cause of the condition.
Regeneron Pharmaceuticals won approval Thursday for its gene therapy for hearing loss, completing what has for nearly a decade been a milestone in the making—for the company and gene therapy more broadly.
Otarmeni, which was approved under the FDA’s Commissioner’s National Priority Voucher (CNPV) program, is intended for individuals with congenital deafness caused by a deficiency of the otoferlin protein, which is critical to the hearing process. It is the first treatment to address an underlying cause of hearing loss and Regeneron’s first approved gene therapy. The company will provide Otarmeni for free in the U.S.
The company has “a lot invested in” the modality, Aris Baras, senior vice president and general manager at the Regeneron Genetics Center, told BioSpace prior to Otarmeni’s approval. Otarmeni is “really our first foray” into genetic medicine, Baras said. Regeneron currently does not list any other gene therapy assets in its pipeline, but the company has published preclinical data in other organs.
Regeneron supported the application for Otarmeni, formerly DB-OTO, with data from the pivotal Phase 1/2 CHORD study, in which 11 out of 12 participants experienced “clinically meaningful” hearing improvements, the company reported in an October press release. Three patients achieved normal hearing levels.
“What is more exciting than seeing a child hear their mother’s voice for the first time?” Jonathon Whitton, vice president at Regeneron Genetic Medicines, told BioSpace prior to the FDA’s greenlight. “That’s beautiful.”
CHORD enrolled 12 subjects with profound hearing loss due to variants of the OTOF gene—nine of whom received DB-OTO in one ear, while three others were treated with the gene therapy in both ears. Whitton recounted the story of one mother, who, standing behind her child, clapped her hands, “and the child pops around to look, and the mother just, you know, freaks out, as you might imagine.”
This was three weeks after the infusion of DB-OTO, Whitton said. “A few more months in, the child can now hear whispers, so they actually have normal hearing sensitivity.” Children develop considerably in the 2- to 3-year age range, added Whitton, who has a young daughter himself. “So getting to see some of these parents experience that explosion of language in their children after they’re hearing for the first time, it’s just, it’s a beautiful thing.”
A litany of firsts
Otarmeni’s approval marks a host of firsts—for Regeneron, for the hearing loss community and for gene therapy.
In addition to its other accolades, Otarmeni is the first gene therapy to not cause any serious adverse events in a clinical trial, according to Eliot Shearer, a pediatric otolaryngologist and investigator for CHORD at Boston Children’s Hospital. “The only adverse events noted were related to the surgery,” Shearer told BioSpace prior to the approval.
The approval is also a boon for gene therapies directly delivered to organs, and not systemically, with high accumulation in the liver, Baras said. Otarmeni involves a single injection of a viral-vectored gene therapy delivered into the cochlea—a part of the inner ear that converts sound vibrations into nerve signals for hearing—under general anesthesia. “What we’re trying to do is use great scientific technology, molecular biology . . . to target gene therapies, to target these viruses to different organs and tissues,” Baras said.
The company has published preclinical data that, according to Baras, proves this concept in muscle and the central nervous system. “We’d love to expand that technology platform to . . . the heart, to other places as well,” he said.
At Regeneron, hearing loss is another big focus, and Baras said Otarmeni is just the beginning. “We’ve always had this dream, this vision, that we could do a lot in a space like hearing loss,” Baras said. Otarmeni is a game-changer for babies with this ultra-rare genetic defect but doesn’t help the 1 in 500 infants that are born in the U.S. with hearing loss stemming from other causes.
“Hearing loss is a big problem for a lot of people,” said Baras, explaining that Regeneron wants to target other types of hearing loss with other modalities, such as an antibody or siRNA therapeutic. Both of these modalities are a key part of Regeneron’s robust “toolbox” of therapeutic approaches, he added.
Otarmeni’s approval “shows that we can do something that we weren’t sure was possible: restore kind of complete loss of hearing to normal hearing.”
Shearer added that lessons learned during Otarmeni’s development will inform future gene therapies for hearing loss. “No one has ever tried to use a viral vector to target the cells of the inner ear before. No one has done this surgery before for humans, so all these things that we’re learning right now are going to be applicable for future gene therapies.”
Right behind Regeneron, Eli Lilly is developing AK-OTOF, another otoferlin targeted gene therapy for hearing loss. In January 2024, Lilly announced that AK-OTOF restored the hearing of a child with profound hearing loss within 30 days of administration in a Phase 1/2 trial. That trial is set to wrap up in October 2028.
Otarmeni, meanwhile, will be available to families right away, Whitton said, though as of April 8, Regeneron was still determining the gene therapy’s price tag.
Ultimately, Thursday’s approval is “a really big win for a small number of patients . . . [a] remarkable type of result that we could have only imagined,” Baras said. “But there’s a lot of bigger next mountains we have to climb.”
