Durable hearing gains from multicenter AAV1-hOTOF gene therapy for OTOF-related deafness

In a multicenter, single-arm trial across eight centers, 42 participants with autosomal recessive OTOF-related congenital deafness received AAV1-hOTOF at three doses. No dose-limiting toxicities were observed, and 90% of treated ears achieved hearing recovery with progressive, durable improvements in ABR/ASSR thresholds and speech perception up to 2.5 years. Younger participants showed greater gains, and baseline DPOAE strength and certain OTOF variants predicted better outcomes, supporting broad efficacy and safety of the therapy over up to 2.5 years.