Main Theme: Otology
Introduction: The otoferlin gene (OTOF) encodes otoferlin, a protein critical for signaling at the inner hair cell synapse. Individuals with OTOF-mediated hearing loss typically present with congenital, severe to profound sensorineural hearing loss, with preserved otoacoustic emissions early in life. Recent advances in gene therapy and intracochlear delivery support the potential to restore physiologic hearing in individuals with OTOF-mediated hearing loss using a one-time, local administration of AK-OTOF (AAVAnc80-hOTOF). The objective of this gene therapy trial for OTOF-mediated hearing loss is to assess the safety, tolerability, and preliminary efficacy of escalating doses of AK-OTOF.
Methods: Clinical trial participants have profound hearing loss, as assessed by auditory brainstem response (ABR), at baseline and receive a one-time intracochlear administration of AK-OTOF using a minimally invasive transcanal approach and the Akouos Delivery Device. Safety assessments and auditory function tests, including ABR and behavioral audiometry, are performed over the trial and long-term follow-up period.
Results: The preliminary safety profile is favorable, with no related serious adverse events and no adverse events related to AK-OTOF gene therapy or the Akouos Delivery Device. Initial clinical evidence shows that AK-OTOF gene therapy has the potential to restore physiologic hearing in individuals with OTOF-mediated hearing loss. Safety and efficacy data from participants will be presented.
Conclusion: Available data suggest that AK-OTOF may be safely administered to participants, with onset of restoration of physiologic hearing as early as one month following administration.