Regeneron Pharmaceuticals said that its investigational gene therapy DB-OTO has improved hearing in two young children with profound genetic deafness in the ongoing Phase 1/2 CHORD trial.

DB-OTO is a cell-selective, adeno-associated virus (AAV) gene therapy candidate. It is designed to offer durable, physiological hearing to those with profound, congenital hearing loss caused by variants of the otoferlin gene.

The gene therapy candidate secured orphan drug, rare paediatric disease, and fast track designations from the US Food and Drug Administration (FDA) and orphan drug designation from the European Medicines Agency (EMA).

CHORD, which is a first-in-human, multicentre, open-label, two-part trial, assessed the safety, tolerability, and preliminary efficacy of DB-OTO in infants, children, and adults with otoferlin variants.

Currently, the CHORD trial is enrolling infants and children across sites in the US, the UK, and Spain.

In the trial, one child was dosed at 11 months of age within 24 weeks, and the second child was dosed at four years of age at a six-week assessment.

During the trial, each child underwent a single intracochlear injection of DB-OTO in one ear. Hearing enhancements were evaluated using pure tone audiometry (PTA) and auditory brainstem response (ABR) tests.

After treatment with the investigational therapy, both children exhibited auditory responses during the initial efficacy assessment at four weeks.

DB-OTO improved hearing to normal levels in the first child and showed initial hearing improvements in the second child.

The first patient demonstrated an average 84dB improvement from baseline across key speech frequencies. Overall, there was an average 80dB improvement across all tested frequencies compared to the baseline.

The second participant showed initial hearing improvements at the six-week follow-up. The child demonstrated behavioural responses to loud sounds.

Additionally, the average improvement from baseline across key speech frequencies was observed around 19dB.

Clinical trial investigator and Columbia University’s Department of Otolaryngology – Head & Neck Surgery chair Lawrence Lustig said: “These impressive results showcase the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related deafness, and we are excited to see how this translates into an individual’s development, especially since early intervention is associated with better outcomes for speech development.”