Gene therapies targeting hearing loss are showing positive results, according to several experts and recent trial outcomes reported on Mar. 23. While the gene therapy sector has faced challenges, including patient deaths and regulatory hurdles, treatments for hereditary deafness are progressing with encouraging data.
The significance of these advances is notable as there are currently no available treatments for congenital deafness affecting about one in 500 infants in the United States each year. Genetic causes account for more than half of these cases, making them prime candidates for gene-based interventions.
Regeneron and Eli Lilly are leading efforts to develop gene therapies aimed at restoring hearing by addressing otoferlin deficiency—a key protein necessary for auditory function. Regeneron's DB-OTO showed “clinically meaningful” improvements in a Phase 1/2 trial, while Lilly’s AK-OTOF restored hearing in a child earlier this year. "The stage is set to make an impact in the auditory area with gene therapies over the next decade," Jonathon Whitton, vice president and global program head for Genetic Medicines at Regeneron, said.
A spokesperson from Lilly explained that their therapy delivers a functional copy of the otoferlin gene: "Millions of individuals worldwide have disabling hearing loss because one of their genes generates an incorrect or incomplete version of a protein [otoferlin] the ear requires for hearing." The spokesperson added that AK-OTOF enables “durable expression of functional otoferlin protein to the inner hair cells of the cochlea.”
Experts say that localized delivery to the ear minimizes risks associated with adeno-associated virus (AAV) vectors used in systemic applications—risks highlighted by safety issues elsewhere in gene therapy development. Graig Suvannavejh from Mizuho Securities noted that local administration reduces toxicity concerns compared to systemic approaches.
Looking ahead, both companies anticipate further developments: Lilly’s study will conclude by October 2028 and Regeneron expects a regulatory decision on DB-OTO within months. As Whitton put it: “There is something powerful about the broader momentum that progress creates... A meaningful result in one area... can show the field what is possible and gives others confidence to take similar chances.”
