Gene Therapy Restores Hearing in Deaf Children

Regeneron Pharmaceuticals has reported promising results from its experimental gene therapy, DB-OTO, which is designed to address profound genetic deafness from birth. The company shared its findings at the 2024 American Society of Gene & Cell Therapy annual meeting in Baltimore. In a significant breakthrough, two young children who received the treatment demonstrated significant improvements in hearing.

One of the children, treated at 11 months, showed a remarkable return to normal hearing levels within 24 weeks, as measured by auditory brainstem response (ABR) and pure tone audiometry (PTA). These are recognized methods for assessing hearing capabilities. The child exhibited an average improvement of 84 decibels across key speech frequencies, with one frequency reaching as low as 10 decibels.

The second child, who received the gene therapy at the age of four, showed initial signs of hearing improvement after six weeks. Behavioral responses to loud sounds were observed, with an average improvement of 19 decibels across speech frequencies.

Dr. Lawrence Lustig, a study investigator and head of Columbia University's Otolaryngology-Head & Neck Surgery department, lauded the results as "impressive" and indicative of DB-OTO's potential to revolutionize the treatment of otoferlin-related deafness.

The positive results stem from the ongoing Phase I/II CHORD trial, an open-label, first-in-human study that is still enrolling participants from the U.S., U.K., and Spain. The trial not only evaluated the efficacy of DB-OTO but also its safety, which was found to be well-tolerated with no serious adverse events related to the treatment.

DB-OTO is a cell-selective, AAV-delivered gene therapy administered via a single subretinal injection. It delivers a functional copy of the otoferlin gene, which is typically mutated and nonfunctional in individuals with genetic hearing loss. Congenital hearing loss, affecting nearly 1.7 out of every 1,000 children born in the U.S., represents a significant medical need, with the otoferlin gene implicated in approximately half of the cases.

Regeneron's early findings from the CHORD trial are in line with other recent advancements in the field. Eli Lilly reported in January 2024 that its otoferlin gene therapy, AK-OTOF, restored the hearing of an 11-year-old boy within a month of treatment. Additionally, a Chinese research team published in The Lancet their success in restoring hearing in five out of six children treated with their otoferlin gene therapy.

These studies, including CHORD, focus on patients with profound genetic deafness since birth, highlighting the potential of gene therapy to transform the lives of those affected by this condition. The developments underscore the ongoing progress and promise of gene therapy in addressing congenital hearing loss.