FDA Approves First Gene Therapy for Hereditary Hearing Loss

The FDA has approved the first gene therapy for DFNB9 hereditary hearing loss, which corrects mutations in the OTOF gene responsible for 2-8 percent of genetic deafness cases in newborns. The therapy involves injecting a neutralized virus carrying a normal OTOF gene copy into the inner ear fluid, based on clinical trial results from 42 participants aged nine months to 32 years treated at eight centers across China. Ninety percent of recipients experienced hearing improvement, with half reaching normal hearing levels by the 2½-year study endpoint, and patients 18 and younger showed the strongest gains. The research team at Mass Eye and Ear, Harvard Medical School, and Fudan University is now adapting the platform to treat GJB2 gene mutations, the most common cause of genetic hearing loss, while pursuing regulatory approval in China.

Gene therapy treatment mechanism and clinical trial results

• ▪The OTOF gene mutation is responsible for between 2 percent and 8 percent of genetic deafness cases in newborns
• ▪The OTOF gene therapy trial participants were treated at eight trial centers across China
• ▪The gene therapy for DFNB9 hereditary hearing loss corrects mutations in the OTOF gene
• ▪The DFNB9 gene therapy involves injecting a neutralized virus carrying a normal copy of OTOF into the fluid of the inner ear
• ▪The OTOF gene therapy research was published April 22 in Nature
• ▪The OTOF gene encodes the otoferlin protein, which is active in the cochlea of the inner ear
• ▪The OTOF gene therapy clinical trial involved 42 participants carrying the OTOF mutation and ranging in age from nine months to 32 years
• ▪The OTOF gene therapy caused no serious adverse events among participants and no dose-related toxicity among groups that received three different doses

Patient outcomes and hearing recovery timeline

• ▪90 percent of OTOF gene therapy recipients saw their hearing improve
• ▪Patients 18 and younger receiving OTOF gene therapy saw the strongest gains in hearing and ability to recognize speech
• ▪Half of OTOF gene therapy recipients reached normal hearing levels by the study's end at 2½ years
• ▪Hearing improvement from OTOF gene therapy was rapid over the first six weeks and plateaued around 26 weeks
• ▪The OTOF gene therapy research builds on research published in 2024 that piloted the therapy among a small number of children
• ▪Hearing recovery from OTOF gene therapy was maintained through 2½ years of follow-up

Future applications and regulatory pathway

• ▪The OTOF gene therapy team is beginning to explore regulatory requirements for the treatment to be approved for use in the clinic, starting in China
• ▪The OTOF gene therapy research team is modifying the platform to treat deafness due to mutations in the GJB2 gene
• ▪The GJB2 gene mutation is the most common cause of genetic hearing loss
• ▪The OTOF gene therapy was conducted by researchers at Mass Eye and Ear, Harvard Medical School, and Fudan University, with additional trial sites in China
• ▪The OTOF gene therapy work is supported by the Chinese and Shanghai governments and Fudan University