Travis Smith was a very serious baby. Born completely unable to hear, his mother, Sierra, struggled to see his personality shine through his mute world.
“My son was 100% deaf,” Smith told Fierce Biotech. “Didn't say mama, didn't even know he had a name.”
But that all changed last June, when Travis had surgery to receive an experimental gene therapy from Regeneron Pharmaceuticals called DB-OTO. Just a few months later, Travis’ world started to sing with sound—literally.
“He loves playing his little guitar. He loves listening to Bruno Mars,” Smith said of her now two-and-a-half-year-old son. “I'm so excited for him to say his first word.”
Now, many more children like Travis may be able to hear their names and jam out to “I Just Might.” The FDA today approved Regeneron’s DB-OTO as Otarmeni, the first gene therapy for the rare genetic form of hearing loss that Travis was born with. And the company plans to give its revolutionary therapy away for free.
“Otarmeni is a huge scientific leap and is representative of Regeneron’s approaches to continually push the boundaries of science to benefit humanity,” George Yancopoulos, M.D., Ph.D., Regeneron’s president and chief scientific officer, said in an April 23 release. “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.,” which the executive said “serves to highlight our belief that the biopharmaceutical industry can be a genuine force for good in the world.”
With the landmark approval of a hearing-loss gene therapy, Regeneron is embarking on a new era marked by a strategic focus on genetic medicines. Otarmeni is both the first approved gene therapy for Regeneron and the first gene therapy approved under the controversial Commissioner's National Priority Voucher program.
“Regeneron is known as an antibody company or biologics company,” Jonathon Whitton, Ph.D., head of the New York pharma’s genetic medicines program, told Fierce Biotech in advance of Otarmeni’s approval. “But for the last eight years, we've been building out our expertise across genetic medicine modalities.”
The inspiration for Otarmeni came from Whitton’s experience as an audiologist, where over the last 20 years, the field has come to understand why some children are born with an inherited form of hearing loss. The key missing protein is otoferlin, which sits at the base of sensory hair cells and helps transmit sound waves to the brain.
“This protein is critical. It’s like the linchpin to enable communication between the sensory cell and the nerve,” Whitton explained. Regeneron’s approach, acquired from its $109 million Decibel Therapeutics buyout in 2023, is to use a viral vector to deliver a functional copy of the otoferlin gene into the ear.
Otarmeni can be delivered using the same surgery as cochlear implants, the current standard of care for children born with this form of hearing loss.
Regeneron previously reported that the therapy improved hearing in 10 of 11 patients in the phase 1/2 Chord trial, which the company then updated to nine of 12 patients, hitting the trial’s primary endpoint for hearing improvement.
“We're really proud of what we're seeing” with Otarmeni, Whitton said, and Regeneron has been building a commercial team around the therapy so that it is ready to launch “day one.”
Only around 20 to 50 children are born with otoferlin-driven hearing loss each year, including Travis. The condition requires inheriting two faulty copies of the otoferlin gene, one from mom and one from dad.
“We went to a ton of audiologists over the first couple months, and they were all very puzzled,” Travis’ mother, Sierra, told Fierce. Nobody else in the family is deaf, and genetic hearing loss is so rare that she had to advocate fiercely to get Travis tested for it at all.
“He had jaundice. He was premature. There's probably a million other reasons why he's deaf,” Smith recalled the doctor saying. But sure enough, when her pushing finally resulted in a genetic test, Smith was right. And after reaching out to as many doctors as she could find and “a million screening tests,” Travis was able to enter Regeneron’s trial.
A new beginning
It took 20 years from the time of Regeneron’s 1988 founding until its first medicine, the interleukin-1 blocker Arcalyst, was approved for a group of rare inflammatory diseases in 2008. With that as a baseline, the pharma’s first gene therapy approval after eight years of work is speedy.
The effort to build up a genetic medicine portfolio began in earnest with a collection of collaborations, Whitton said, spanning multiple modalities and with many different early-stage biotechs. Decibel Therapeutics, where Whitton headed up R&D at the time, was one of them.
“I was working with Regeneron basically the entire time,” Whitton recalled. “We had to do everything from the beginning on really building out these technologies together.”
By working with many different partners, Regeneron was able to piece together a plan of which programs represented a viable future in genetic medicines, he said.
“You get the right strategic partnerships, you do the internal build of your own capabilities to operate within these spaces,” Whitton said. “Once you're ready to start bringing these things into clinical trials, you do the same thing in terms of the internal build of your development staffing.”
Regeneron has now reached the final step of this process with Decibel, building a commercial team that is ready to roll out Otarmeni and related products that come down the line.
While Otarmeni is a gene therapy, Regeneron’s pipeline reflects a wide array of genetic approaches, including gene editing and RNA-based gene silencing tools. And while these programs span a wide range of therapeutic areas, the company is also committed to hearing loss, with an internal research team fully committed to understanding the biology of how adults can lose hearing over time.
“If you think about acquired hearing loss, age-related hearing loss or noise-induced hearing loss, these are millions and millions of people who are dealing with this,” Whitton said. “One of the challenges is people don't really understand the biology very well of exactly what's causing hearing loss.”
“We're making significant investments into deeply understanding the biology of these acquired forms of hearing loss so that we can also develop medicines in the same way we did with DB-OTO,” he added, with antibodies and siRNAs on the table as well as gene therapies.
While Regeneron hopes Otarmeni becomes just one piece of a genetic medicine franchise, the therapy has already restored Sierra Smith’s hopes for her son, Travis, all by itself. She recalled taking Travis to an event organized by Hands & Voices, a non-profit that supports deaf and hard-of-hearing children, before his treatment.
“I broke down crying, because there's all these beautiful little children with hearing aids and cochlear implants, and all of them can hear to some extent and communicate,” Smith said. But Travis wasn’t eligible for any of these devices, she said, and she worried about him being lonely. “He should fit in with all these kids, but he was different.”
But now with his hearing restored by Otarmeni, Travis should be able to get hearing aids down the line, and Smith is optimistic about his future.
“I see all these other children and adults with hearing aids, and they live normal lives, and they still get the same opportunities as everybody else,” Smith said. “I think he's going to be okay.”