Efficacy and safety of SENS-501, a dual-AAV otoferlin gene therapy, for DFNB9 congenital deafness

mice achieved targeted expression of otoferlin specifically in cochlear inner hair cells (IHCs), resulting in the restoration of auditory function observed as early as 3 weeks post administration and sustained for up to 10 months. SENS-501 was well tolerated following both local and systemic administrations in wild-type mice. GLP toxicology studies in non-human primates using the same surgical method and injection device used in DFNB9 patients confirmed that the intracochlear administration of SENS-501 is well tolerated and affords an adequate safety margin for human use. Vector biodistribution was largely restricted to the injection site. Collectively, these preclinical data support the development of SENS-501 as a safe and efficacious AAV-based treatment for DFNB9. A phase 1/2 clinical trial in children with severe-to-profound hearing loss due to otoferlin mutations is underway.