Travis Smith was a very serious baby. His mother, Sierra, who was born completely deaf, struggled to see his personality shine through in a silent world.
“My son was 100% deaf,” Smith told Fierce Biotech. “I didn’t say Mama, and I didn’t even know she had a name.”
But that all changed last June when Travis underwent surgery to undergo Regeneron Pharmaceuticals’ experimental gene therapy DB-OTO. Just a few months later, Travis’ world literally started singing.
“He loves playing his little guitar. He loves listening to Bruno Mars,” Smith said of her son, now 2 1/2 years old. “I’m really looking forward to hearing his first words.”
Now, even more kids like Travis may be able to hear their name and play “I Just Might.” The FDA today approved the company’s DB-OTO as Otalmeni, the first gene therapy for the rare genetic hearing loss that Travis was born with. And Regeneron plans to offer its innovative treatment for free.
“Otarmeni is a major scientific advance and represents Regeneron’s approach to continually pushing the boundaries of science to benefit humanity,” George Yancopoulos, MD, 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 offer these gene therapy advances for free to the American people,” the executive said. “This underscores our belief that the biopharmaceutical industry can be a force for real benefit for the world.”
With the landmark approval of its hearing loss gene therapy, Regeneron is embarking on a new era marked by a strategic focus on genetic medicines. Otarmeni is the first gene therapy approved for Regeneron and also the first gene therapy approved under the Secretary’s controversial National Priority Voucher Program.
“Regeneron is known as an antibody company or a biopharmaceutical company,” Dr. Jonathon Whitton, head of the New York drugmaker’s genetic medicines program, told Fierce Biotech ahead of Otarmeni’s approval. “But over the past eight years, we have built expertise across the spectrum of genetic medicine.”
Otarmeni’s inspiration came from Whitton’s experience as an audiologist. Over the past two decades, the field has come to understand why some children are born with inherited hearing loss. The key protein missing is otoferlin, which is present at the base of sensory hair cells and helps transmit sound waves to the brain.
“This protein is important. It’s like the linchpin that allows communication between sensory cells and nerves,” Whitton explained. Regeneron, which acquired Decibel Therapeutics for $109 million in 2023, uses a viral vector to deliver a functional copy of the otoferlin gene to the ear.
Otarmeni can be delivered using the same surgery as a cochlear implant, the current standard treatment for children born with this type of hearing loss.
Regeneron previously reported that the therapy improved hearing in 10 of 11 patients in the Phase 1/2 CHORD trial, but the company has since updated that 9 of 12 patients met the trial’s primary endpoint of improved hearing.
“We’re really proud of what we’re seeing” with Otarmeni, Whitton said, noting that Regeneron is building a commercial team around the therapy to be ready to launch on “day one.”
Only about 20 to 50 children are born with otopherin-induced hearing loss each year, including Travis. This condition requires inheriting two defective copies of the otoferlin gene, one from the mother and one from the father.
“For the first few months, we visited a lot of audiologists and they were all very confused,” Travis’ mother Sierra told Fierce. Because no one in her family is deaf and hereditary hearing loss is extremely rare, she had to insist that Travis get tested.
“He had jaundice. He was born prematurely. There’s probably a million other reasons why he couldn’t hear,” Smith recalled doctors saying. But sure enough, Smith was right when her push finally led to genetic testing. After contacting as many doctors as possible and performing “a million screening tests,” Travis was able to enroll in the Regeneron trial.
new beginning
Regeneron was founded in 1988, and it took 20 years for its first drug, the interleukin-1 inhibitor Arcalist, to be approved in 2008 to treat a group of rare inflammatory diseases. Taking this as a baseline, the approval of the company’s first gene therapy drug, after eight years of work, is a quick one.
Whitton said the effort to build the genetic medicine portfolio began in earnest with a series of collaborations with a variety of early-stage biotechs across multiple modalities. One of those companies was Decibel Therapeutics, where Whitton was leading research and development at the time.
“I basically worked with Regeneron all the time,” Whitton recalls. “We had to do everything from scratch to actually build these technologies.”
By working with many different partners, Regeneron was able to put together a plan for what programs could be a viable future for genetic medicines, he said.
“We can get the right strategic partnerships and build our own capabilities internally to operate within these areas,” Whitton said. “Once we’re ready to bring these things into clinical trials, we’ll do the same thing in terms of building out our development staff internally.”
Regeneron has now reached the final stage of this process with Decibel and is building a commercial team ready to deploy Otarmeni and related products in the future.
Dr. Jonathan Whitten (Regeneron Pharmaceuticals)
Although Otarmeni is a gene therapy, Regeneron’s pipeline reflects a wide range of genetic approaches, including gene editing and RNA-based gene silencing tools. While these programs span a wide range of treatment areas, the company also has a strong focus on hearing loss, and its in-house research team is dedicated to understanding the biology of how adults lose hearing over time.
“If you think about acquired hearing loss, age-related hearing loss, noise-induced hearing loss, millions of people suffer from this hearing loss,” Whitton said. “One of the challenges is that people don’t really understand the biology of exactly what causes hearing loss.”
“We are investing heavily in deeply understanding the biology of these acquired hearing losses so that we can develop medicines in the same way we did with DB-OTO,” he added, and is considering gene therapy as well as antibodies and siRNA.
Regeneron hopes Otalmeni will become just one part of a genetic medicine franchise, but the treatment has already restored Sierra Smith’s hopes for her son Travis on its own. She recalled that before Travis’ treatment, she took him to an event hosted by Hands and Voice, a nonprofit organization that supports hearing-impaired children.
“I burst into tears because all these beautiful little children with hearing aids and cochlear implants can hear and communicate to some extent,” Smith said. But Travis didn’t qualify for these devices and she feared he would be alone. “He should fit in with all these kids, but he wasn’t.”
But with Otarmeni restoring his hearing, Travis should be able to get hearing aids in the future, and Smith is optimistic about his future.
“I see other children and adults wearing hearing aids, and they’re living a normal life and still getting the same opportunities as everyone else,” Smith said. “I think he’ll be fine.”
