Regeneron's Gene Therapy Shows Promise in Restoring Hearing for Rare Genetic Condition

Regeneron Pharmaceuticals has made significant strides in the treatment of otoferlin-related deafness, a rare genetic condition, with its investigational gene therapy DB-OTO. The latest data from the Phase I/II CHORD trial, presented at the Association for Research in Otolaryngology's 48th Annual MidWinter Meeting in Orlando, Florida, demonstrates notable hearing improvements in the majority of treated children.

Promising Clinical Results

The CHORD trial, involving 12 participants aged between 10 months and 16 years, has shown encouraging outcomes. Ten out of 11 children with at least one post-treatment assessment demonstrated significant hearing improvement at various decibel levels. Remarkably, three out of five children with 24-week assessments experienced improvements bringing their hearing to "nearly normal" or "normal" levels.

One particularly striking case involved the first patient dosed, who received treatment at 10 months of age. New 72-week results reveal substantial progress in speech and development, with the child now able to correctly identify words at a conversational level without visual cues.

Dr. Jonathon Whitton, Regeneron's vice president and auditory global program head, highlighted the rapid onset of efficacy: "You can see the efficacy very early on. We are actively talking to FDA and other agencies around the world to understand what the clinical data set [is] but also everything else that you need to put together for your package to eventually get a drug approved."

Treatment Mechanism and Safety Profile

DB-OTO, acquired by Regeneron through its $109 million purchase of Decibel Therapeutics in 2023, is a cell-selective AAV gene therapy. It delivers a cDNA molecule coding for the normal otoferlin protein sequence, creating an "protein factory" in the cell that continuously produces the protein at a specific level in inner hair cells.

The treatment is administered via an intracochlear injection using a surgical procedure similar to cochlear implantation. This approach was chosen to allow for intervention in very young patients, as early treatment is crucial for maximizing outcomes in congenital deafness.

Safety data from all 12 patients indicate that both the surgical procedure and DB-OTO have been well-tolerated. No adverse events directly caused by DB-OTO have been reported, although some patients experienced transient post-surgical vestibular effects that resolved within six days of dosing.

Industry Landscape and Future Prospects

Regeneron is not alone in targeting otoferlin-related deafness. At least four other companies, including Eli Lilly (through its acquisition of Akouos Inc.), Sensorion, and Refreshgene Therapeutics, are developing similar gene therapies. This growing interest underscores the potential of gene therapy in addressing genetic causes of hearing loss.

Dr. Christos Kyratsous, Regeneron's senior vice president and co-head of genetic medicines, emphasized the company's commitment to gene therapy despite recent setbacks in the field: "We truly believe in the power of these technologies—we believe in what they can do for patients. So, we are trying to adopt the long-term view, as we do for most of the technologies we are working on."

While otoferlin-related deafness affects a relatively small population—estimated at 10,000 to 20,000 people in the U.S.—researchers are optimistic about the potential of gene therapies for other sensory disorders. Regeneron is already exploring treatments for GJB2-related hearing loss, which affects about 1,400 children in the U.S. annually.

As the field of genetic medicine continues to evolve, these advancements in treating rare forms of hearing loss may pave the way for broader applications in addressing more common auditory conditions, potentially transforming the landscape of hearing loss treatment.