Regeneron Pharmaceuticals announced updated data for its investigational gene therapy, DB-OTO, from a phase 1/2 trial in 12 children who have profound genetic hearing loss due to variants of the otoferlin (OTOF) gene.

DB-OTO is an investigational 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 to replace the faulty OTOF gene using a modified, non-pathogenic virus that is delivered via an injection into the cochlea under general anesthesia (similar to the procedure used for cochlear implantation).

To date, 12 participants in the phase 1/2 CHORD trial have received DB-OTO — nine were administered an intracochlear injection in one ear and three received it bilaterally (both ears). The data shared by Regeneron include 72-week results showing speech and development progress in the first child dosed at 10 months of age, as well as initial results in 11 children (aged 10 months to 16 years old), three of whom received DB-OTO bilaterally.

Among the 11 participants with at least one post-treatment assessment, 10 demonstrated a notable response, with improved hearing at various decibel hearing levels (dBHL). Additionally, among five participants with 24-week assessments, three experienced improvements in average hearing thresholds to “nearly normal” (≤40 dBHL) or normal (≤25 dBHL) hearing levels. Only one participant has not experienced a change from their baseline hearing at 24 weeks post-dosing.

Across all 12 participants, both the surgical procedure and DB-OTO were well tolerated, and there were no adverse events or serious adverse events considered related to DB-OTO.

DB-OTO has Orphan Drug, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy designations from the U.S. FDA and Orphan Drug designation from the European Medicines Agency.