DB-OTO Trial: Profound Deafness Reversed in Child, Early Improvements in Another

Regeneron Pharmaceuticals, Inc. recently announced promising findings from their ongoing Phase 1/2 CHORD trial, which is examining the investigational gene therapy DB-OTO. This therapy showed significant hearing improvement in one child treated at 11 months, who became one of the youngest patients globally to receive gene therapy for genetic deafness. Preliminary data were shared during an oral presentation at the American Society of Gene and Cell Therapy (ASGCT) annual conference.

The CHORD trial, currently enrolling infants and children in the U.S., UK, and Spain, investigates DB-OTO's potential to treat profound genetic deafness caused by otoferlin gene variants. The trial involves a single intracochlear injection of DB-OTO, a method similar to cochlear implants, making it viable for very young patients. Both pure tone audiometry (PTA) and auditory brainstem response (ABR) are used to evaluate hearing improvements.

One of the trial's significant findings included a child dosed at 11 months showing normal hearing levels within 24 weeks. This child exhibited an average 84-decibel improvement from baseline and one frequency reaching a 10-decibel hearing level as measured by PTA. The ABR results showed positive responses, with the best frequency reaching 45 decibels. Another child, dosed at four years, also showed initial hearing improvements at a six-week assessment. This child demonstrated an average 19-decibel improvement from baseline, with one frequency reaching an 80-decibel hearing level, and the best ABR frequency reaching 75 decibels.

Both children tolerated the surgical procedure and DB-OTO well, with no adverse or serious adverse events reported post-treatment. These results underscore DB-OTO's potential as a revolutionary treatment for otoferlin-related deafness, providing a beacon of hope for early intervention in congenital hearing loss, which is critical for better speech development outcomes.

DB-OTO has received various designations, including Orphan Drug, Rare Pediatric Disease, and Fast Track from the U.S. Food and Drug Administration, and Orphan Drug status from the European Medicines Agency. These designations reflect the therapy's promise in addressing the underlying genetic causes of hearing loss.

Otoferlin-related hearing loss, an ultra-rare genetic condition, affects the communication between the sensory cells in the inner ear and the auditory nerve due to faulty otoferlin protein production. While traditional devices like hearing aids and cochlear implants amplify sound, they do not restore the complete spectrum of sound. DB-OTO represents a significant advancement, potentially offering physiological hearing by delivering a functioning version of the otoferlin gene to the affected cells via a modified, non-pathogenic virus.

The CHORD trial, a multicenter, open-label study, evaluates the safety, tolerability, and preliminary efficacy of DB-OTO in patients under 18 years old with otoferlin gene variants. The trial is conducted in two parts: an initial dose-escalation cohort and an expansion cohort, the latter involving simultaneous injections in both ears.

Regeneron, a pioneer in biotechnology, emphasizes developing transformative medicines for serious diseases. Their research and clinical programs include a wide array of conditions, notably advancing genetic medicine platforms to find innovative treatments.

The company’s continued commitment to scientific discovery and innovative therapeutic approaches reflects in their proprietary technologies, which aim to transform the treatment landscape for various diseases, including genetic deafness.