Regeneron Advances In Vivo Gene Therapy For Hearing Loss

By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

When the FDA granted accelerated approval to Otarmeni, it marked more than just another regulatory win. For Regeneron, the therapy represents its first approved genetic medicine and a defining moment for in vivo gene therapy in hearing loss.

I had the chance to sit down with Regeneron’s VP Global Program Head Genetic Medicines, Jonathan Whitton, Ph.D., who reflected on the long path to this milestone and what it could mean for patients and the broader field. The therapy targets OTOF-related hearing loss, a rare genetic condition that leaves children born without the ability to transmit sound signals from the ear to the brain. “This is the first medicine for inherited hearing loss, period,” Whitton said. “It’s also the first genetic medicine for a form of inherited hearing loss, so it’s a completely new space.”

For the CGT sector, this approval is important because it shows that in vivo gene therapy can move beyond proof-of-concept and into real-world care for a sensory disorder. It also broadens the conversation around where genetic medicines can make a meaningful difference, particularly in diseases where early intervention can change the entire developmental trajectory.

Just as importantly, Otarmeni highlights how the field is evolving toward more targeted, clinically practical delivery approaches. That combination of biological precision, translational discipline, and patient impact is exactly what CGT has been working toward.

Understanding the Biology Behind the Breakthrough

Whitton’s perspective is rooted in decades of work as a pediatric audiologist and neuroscientist. Early in his career, clinicians could diagnose hearing loss in children but often could not explain its cause. “The truth is that most of the time we could not say why the child had hearing loss,” he said.

That began to change with advances in human genetics. Researchers discovered that many cases of congenital hearing loss stem from specific protein deficiencies caused by inherited mutations. In OTOF-related hearing loss, the missing protein prevents inner ear cells from transmitting sound signals. “When you can actually understand the molecular cause of the condition, you can totally reimagine how you would make medicines,” Whitton explained.

That insight became the foundation for Otarmeni. By delivering the genetic instructions needed to produce the missing protein directly into the affected cells, the therapy aims to restore the natural signaling pathway required for hearing.

“We thought, what if we could deliver the instructions for making that protein into those cells,” Whitton said. “Maybe then these kids could go from having no hearing to having really good hearing.”

From Concept to Clinic

Developing that concept into a viable therapy required nearly a decade of work. Regeneron built a targeted in vivo gene therapy platform using AAV vectors designed to deliver genetic material precisely to the correct cell types in the inner ear. “It’s a precise therapy that’s delivered directly to the cells that need it,” Whitton said.

The company also made a strategic decision to align delivery with existing clinical practice. Surgeons administer the therapy using a procedure similar to cochlear implant surgery, helping ensure familiarity among clinicians. “We wanted providers to be comfortable right away with how they do the delivery,” Whitton noted.

The results from the CHORD clinical trial have been striking. Children who were born with severe to profound hearing loss began responding to sound within weeks of treatment. In many cases, the first signs of success were observed not in the clinic but at home. “The parents are really the first ones to see it,” he said. “They’re at home, and they start to notice their child responding to sound.”

By six months, some patients achieved normal hearing sensitivity. At one year, 42% of patients reached normal hearing levels, and the majority experienced clinically meaningful improvements that allowed them to hear speech without assistive devices. “No one has ever seen this before,” Whitton said. “You take a neurosensory function and go from profound loss to normalization in a six-month time frame.”

Expanding the Treatment Window

One of the most surprising findings has been the therapy’s effectiveness beyond early childhood. While researchers initially expected benefits to be limited to very young patients, the data suggest a broader window of opportunity. “We’ve enrolled some children as old as 16 years of age, and we found that they also benefited,” Whitton said.

These older patients showed improvements in both hearing and speech comprehension, challenging long-held assumptions about neurodevelopmental timing in hearing restoration.

“I’m really happy about being wrong about my perception initially about what the window might look like,” he added.

The findings raise the possibility that Otarmeni could benefit not only infants but also adolescents and potentially adults who were previously thought to be beyond the optimal treatment window.

A New Model for Access

Beyond its clinical impact, Otarmeni is drawing attention for an unprecedented decision: Regeneron is offering the therapy free of charge in the United States.

“I don’t know, it’s kind of simple. We’re making the therapy free,” Whitton said.

The decision reflects the company’s broader philosophy and was discussed internally long before approval.

“This comes from our co-founders,” he explained. “They’ve been talking about this for a long time as we were developing the program and seeing the transformational benefits.”

While the therapy itself is provided at no cost, patients may still incur expenses related to the surgical procedure. However, because the delivery approach mirrors cochlear implant surgery, those costs are expected to be covered by insurance in many cases.

Implementing such a model is not without challenges. “It’s no easy task to figure out exactly how to implement a program like this,” Whitton acknowledged. “But that’s what we’re doing.”

Safety and Technology Advancements

Otarmeni also stands out for its safety profile. “We didn’t have any therapy-related adverse findings in this study,” Whitton said.

This is particularly notable in the context of gene therapy, where safety concerns have historically been a major focus.

The therapy also represents a technological milestone as one of the first approved dual AAV vector systems, a strategy designed to deliver larger genetic payloads than traditional single-vector approaches.

The choice of AAV was driven by its ability to effectively target inner ear cells while minimizing systemic exposure. “We thought we could avoid a lot of the issues that often come up with high-dose systemic AAV,” he explained.

What’s Next for Regeneron

For Regeneron, Otarmeni is just the beginning. The company sees this program as both a breakthrough in hearing loss and a proof point for a broader strategy rooted in human genetics. “This is the beginning for us,” Whitton said. “It’s the tip of the iceberg on our translation of genetics into transformational therapies.”

Through efforts like the Regeneron Genetics Center, which has sequenced millions of individuals, the company aims to identify new targets and develop therapies across a wide range of diseases.

“You deeply understand the human genetics, and from that, you get the insights and the biology,” Whitton said. “Then you can develop these transformational therapies.”

As Otarmeni begins to reach patients, its impact will be measured not only in clinical data but in everyday moments. Children hearing their parents’ voices for the first time. Families experiencing milestones once thought impossible. For Whitton and his colleagues, those moments are what define the success of the program.