Regeneron’s Gene Therapy Shows ‘Dramatic’ Hearing Improvement in Deaf Kids

 Regeneron Pharmaceuticals’ investigational gene therapy DB-OTO improved hearing in two young children with “profound genetic deafness” since birth, according to the company’s Wednesday oral presentation at the 2024 American Society of Gene & Cell Therapy annual meeting in Baltimore.

One patient returned to normal hearing levels within 24 of treatment, as measured by auditory brainstem response (ABR) and the gold-standard pure tone audiometry (PTA)—both of which are validated methods of evaluating hearing function. The patient was dosed with DB-OTO at 11 months of age and is “one of the youngest in the world to receive a gene therapy for genetic deafness,” Regeneron said in its news release on Wednesday.

At the 24-week assessment mark, the patient showed an average 84-dB improvement from baseline across key speech frequencies. PTA found that one frequency even reached 10 dB in hearing level.

The second patient, who was given the gene therapy at four years of age, showed “initial hearing improvements” at the six-week follow-up. The patient demonstrated behavioral responses to loud sounds. The average improvement from baseline across key speech frequencies was 19 dB.

Lawrence Lustig, study investigator and chairperson of Columbia University’s Department of Otolaryngology-Head & Neck Surgery, in a statement called these initial results “impressive,” adding that they “showcase the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related deafness.”

Wednesday’s initial readout comes from the ongoing Phase I/II CHORD trial, a first-in-human open-label study, which is still currently enrolling patients from sites in the U.S., U.K. and Spain. In addition to efficacy, CHORD also looked at the safety of DB-OTO and found it to be well-tolerated with no treatment-related serious adverse events.

Designed to be delivered via a single sear injection, DB-OTO is a cell-selective, AAV-delivered gene therapy that works by delivering a functioning copy of the otoferlin gene, which is mutated and dysfunctional in patients with genetic hearing loss. Affecting nearly 1.7 out of every 1,000 children born in the U.S., congenital hearing loss presents a “significant unmet need,” according to Regeneron. The otoferlin gene is implicated in about half of these cases.

With the early results from CHORD, Regeneron follows in the footsteps of Eli Lilly, which in January 2024 revealed that its investigational otoferlin gene therapy AK-OTOF restored the hearing of an 11-year-old boy within 30 days of treatment. A day later, a Chinese research group published results in The Lancet, showing that they were able to restore hearing in five of six children treated with their own otoferlin gene therapy.

As in the case of CHORD, the patients in these two studies had profound genetic deafness since birth.

https://www.biospace.com/article/asgct24-regeneron-s-gene-therapy-shows-dramatic-hearing-improvement-in-deaf-kids/