Regeneron to seek approval of hearing loss gene therapy this year

Regeneron Pharmaceuticals announced that updated data for its investigational gene therapy, DB-OTO, for profound genetic hearing loss due to variants of the otoferlin (OTOF) gene were published in The New England Journal of Medicine and presented during an oral presentation at the annual American Academy of Otolaryngology-Head and Neck Surgery meeting.

The latest results from the pivotal CHORD trial show 11 out of 12 participants have experienced clinically meaningful hearing improvements, including three who achieved normal hearing levels. Additionally, eight participants with longer follow-up showed stability or continued improvement in their hearing, and among three who completed speech assessments, all showed significant improvement.

The CHORD trial evaluated pediatric participants with profound hearing loss due to variants of the OTOF gene that received a single administration of DB-OTO via intracochlear infusion. Among 12 participants (aged 10 months to 16 years), nine received the gene therapy unilaterally (in one ear) and three received it bilaterally (in both ears).

DB-OTO is a cell-selective, dual adeno-associated virus (AAV) vector gene therapy designed to provide durable, physiological hearing to individuals with profound, congenital hearing loss caused by variants of the OTOF gene. The treatment aims to deliver a working copy of the OTOF gene to replace the non-functional otoferlin protein using a modified, non-pathogenic virus that is delivered via an infusion into the cochlea under general anesthesia (similar to the procedure used for cochlear implantation). In the therapy, the newly introduced OTOF gene is under the control of a proprietary cell-specific Myo15 promoter, which is intended to restrict expression only to hair cells that normally express otoferlin.

Regeneron’s U.S. regulatory application for DB-OTO is planned for later this year, pending discussions with the FDA. DB-OTO received orphan drug, rare pediatric disease, fast track and regenerative medicine advanced therapy designations from the FDA. The EMA also granted it orphan drug designation.