Understanding the Real Needs of Families: Advancing Hearing Solutions for Children and Adults

Last month, Regeneron announced updated results from the Phase I/II CHORD trial in children with otoferlin-related hearing loss. Out of 11 children who received DB-OTO, 10 showed notable hearing improvements at different decibel levels, with some achieving nearly normal or normal hearing thresholds. Pharmaceutical Executive spoke with Jonathon Witton, AuD, PhD, VP, auditory global program head, in more detail about the trial results, the performative potential of DB-OTO, and the company’s work with the hearing loss community.

Pharmaceutical Executive: How has Regeneron engaged with the hearing loss community, including patients and clinicians, to understand and optimize DB-OTO’s potential impact?

Jonathan Whitton: Since the beginning of this particular program, we have spent a lot of time talking with clinicians in the field. Obviously, I have been one of them. Our goal is to understand the biggest unmet needs for patients—where we can solve problems for them. We’ve also spent significant time engaging with advocacy groups, the patient community, and families during the early stages, as we were determining where to focus our technology development efforts. I think when you learn about what’s really important to families, the answers can be surprising.

For example, one thing that families talked a lot about was the importance of their children being able to hear 24/7, which is something we often take for granted. We continue to hear even while we sleep. In fact, we sometimes wake up because something alerts us. Our ears play a critical role in our safety. We’ve repeatedly heard from parents that when children are fitted with prostheses for their hearing loss, they often need to remove them for activities like sporting events, and this raises safety concerns for parents.

When I initially thought about these programs, I focused on developing technology to improve speech understanding, noise perception, and the ability to appreciate music. I was looking at all of this complex processing from a scientific perspective. But when I spoke with families, I found that what mattered most to them was ensuring their kids’ safety and being able to hear things like an approaching car. These are insights you gain through early conversations. A key part of our culture is making these personal connections.

Another point worth mentioning is that this is just the beginning for us. We’re starting with a program that impacts a smaller number of patients each year—fewer than 50 children are born annually with deafness caused by a mutation in this specific gene. But we’re not stopping there. We’re committed to continuing the development of these kinds of therapeutics, both for childhood deafness and adult-onset hearing loss.

Deafness can affect individuals early in life, and it also has a significant impact later in life, with noise-induced hearing loss and age-related hearing loss. This is another area we’re investing in, with the goal of developing treatments for these patients as well. I believe it’s a great opportunity to address pressing public health challenges, and we’re excited to lead the way.

Full Interview Summary: Regeneron envisions DB-OTO reshaping the standard of care for hearing loss by shifting from symptomatic management with prostheses, such as hearing aids and cochlear implants, to a molecularly targeted therapeutic approach. Historically, clinicians diagnosed hearing loss without understanding its genetic cause, but advances in genetic testing have revealed that over half of childhood hearing loss cases stem from genetic protein deficiencies. DB-OTO aims to correct this by delivering functional DNA to specific inner ear cells, enabling them to produce the missing protein, potentially restoring hearing to near-normal levels.

The transformative potential of DB-OTO is evident in early clinical trials, where 10 out of 11 patients demonstrated hearing improvements, with some achieving normal or near-normal sensitivity. This represents a paradigm shift—clinicians will now need to incorporate molecular diagnostics into routine care, ensuring that patients receive precise, targeted treatments rather than generalized symptom management.

Regeneron has secured multiple regulatory designations, including the FDA’s RMAT designation, which facilitates early and frequent discussions with regulators. These interactions are crucial in navigating the complexities of gene therapy development, accelerating timelines for approval and commercialization.

Challenges remain, particularly in clinical development and manufacturing. Ensuring scalable, high-quality production of gene therapies is as critical as generating robust clinical data. Regeneron has invested heavily in manufacturing capabilities to meet these demands.

Beyond clinical development, Regeneron actively engages with the hearing loss community, including advocacy groups, clinicians, and families. Insights from these discussions have highlighted practical concerns, such as ensuring continuous hearing for safety. This patient-centric approach shapes the development of DB-OTO and future gene therapies, with plans to expand treatments to broader populations, including adults with age-related and noise-induced hearing loss. Regeneron aims to pioneer gene therapy solutions for a currently untreatable public health challenge.