Fast-Tracking Innovation: The Role of Regulatory Designations in DB-OTO’s Development

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 regulatory authorities.

Pharmaceutical Executive: DB-OTO has received multiple designations from the FDA and EMA—how do these designations accelerate the development and potential commercialization timeline?

Jonathon Whitton: We have received multiple designations from several regulatory agencies. I'll focus on the FDA. One of the most important designations we've received is Regenerative Medicine Advanced Therapy, which is essentially the breakthrough designation for cell and gene therapy. A key benefit of this designation is the opportunity to have additional meetings with the FDA to discuss your development program.

We’re working in a new area of medicine, and we’re trying to pioneer it. It’s crucial to have early, collaborative discussions with regulators to address the challenges in these types of development programs. For a program like DB-OTO, there’s an urgency to move forward for patients with high unmet needs. It's critical to have open, collaborative discussions with regulators about your development plan. I believe that’s the biggest value of these types of designations, as regulatory authorities are quite busy. They have a lot of work to do. When your programs can get in front of them and you have the chance to meet face-to-face and work through issues, it’s incredibly important for accelerating these programs.

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.