Regeneron is presenting findings from two case studies in the CHORD trial of their gene therapy
DB-OTO at the American Society of Gene and Cell Therapy (ASGCT) meeting in Baltimore. This treatment aims to restore hearing in patients with genetic hearing loss caused by mutations in the
otoferlin gene.
The first patient, a baby with distinctive blond hair, was the initial recipient of DB-OTO in this phase 1/2 trial. The child's parents noticed significant improvements in her hearing before the clinical investigators did. According to Jonathon Whitton, Ph.D., executive director and head of Regeneron’s Auditory Global Program, the child began responding to sounds within four weeks of treatment, and by six months, she was reacting to meaningful sounds. At the 24-week mark, she could hear even when her cochlear implant was turned off. Initially enrolled in the trial at eight months old, the child's reliance on the implant has diminished as her natural hearing improves.
The second case in the trial involves a 4-year-old who also showed improvement at similar intervals as the first patient, responding to sound at weeks four and six. Both patients have tolerated the treatment well despite the occurrence of common respiratory illnesses, such as
ear infections, which were manageable with standard care.
Christos Kyratsous, Ph.D., co-head of Regeneron Genetic Medicines, emphasized the remarkable progress achieved with DB-OTO. Conceived during a brainstorming session between Regeneron and
Decibel Therapeutics, the idea took around five to six years to translate into meaningful clinical outcomes. Kyratsous expressed astonishment at the rapid development and significant impact of the treatment.
DB-OTO is an adeno-associated viral (AAV) gene therapy designed for children with
hearing loss due to otoferlin gene mutations. Regeneron's acquisition of Decibel Therapeutics for $109 million last year facilitated the continuation of their collaborative work on DB-OTO, which began in 2017. The therapy functions by delivering cDNA to the ear, which then expresses the missing otoferlin protein in the sensory hair cells. These cells play a critical role in transmitting sound signals from the ear to the brain.
Whitton explained that DB-OTO essentially mimics the common surgical procedure for cochlear implants. This familiarity could ease the adoption process if DB-OTO reaches the market, as surgeons are already accustomed to the surgical techniques involved.
A significant observation from the first patient’s family was that the child's voice became less "screechy" when the cochlear implant was not in use, hinting that DB-OTO might offer a more natural hearing experience. Unlike cochlear implants, which bypass the ear to send signals directly to the auditory nerve, DB-OTO aims to restore the ear's natural ability to transmit sound to the brain.
Regeneron conducted rigorous preclinical tests to assess the durability of DB-OTO's effects, and they are optimistic that the restored hearing will be long-lasting. Since the targeted hair cells do not regenerate, the therapy could provide a permanent solution if successful.
The clinical trial is ongoing, and Regeneron is continuing to enroll patients to gather more data on DB-OTO's effectiveness and durability. The promising early results have set a hopeful tone for the future of gene therapy in addressing genetic hearing loss.
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