Regeneron Reports Initial Positive Results from Phase 1/2 CHORD Trial of DB-OTO Gene Therapy in Pediatric Patient with OTOF-Related Congenital Deafness

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On October 26, Regeneron (NASDAQ: REGN) announced the first patient (under 2 years old) in the Phase 1/2 CHORD trial investigating otoferlin gene therapy (DB-OTO).Preliminary Safety and Efficacy Results Are Promising。

Congenital hearing loss (hearing loss present at birth) represents a significant unmet medical need, with no currently approved pharmacological treatment available. In the United States, approximately 1.7 out of every 1,000 newborns are affected by congenital hearing loss. AlthoughotoferlinHearing loss caused by genetic mutations is extremely rare, but most cases of permanent congenital hearing loss diagnosed in developed countries are sensorineural.Caused by a single gene defect, making it suitable as a target for gene therapy.。

"Consultant Ear Surgeon at Cambridge University Hospitals NHS Foundation Trust and Chief Trial Investigator Manohar BanceThe professor said, "Children participating in the CHORD trial typically have congenital severe hearing loss, which is due toCaused by mutations in a single gene, otoferlin, this mutation essentially shuts down their auditory circuits. Cochlear implants are the current standard of treatment but cannot replicate the full complexity and range of sound. With these very preliminary DB-OTO results, it shows that this gene therapy may help to "turn the switch back on" for these auditory circuits. We look forward to following up further on this child and others to determine whether DB-OTO gene therapy can restore clinically meaningful hearing as they learn to interact with the world."

In the trial, one of the child's ears received an intracochlear injection of DB-OTO. During the planned follow-up, auditory responses improved at week 6 compared to baseline, according to Auditory Brainstem Response (ABR) and behavioral (pure tone) audiometry. ABR is a clinically recognized physiological measurement of auditory sensitivity; typical otophelin-related hearing loss patients usually do not have ABR, and neither did the child’s bilateral ears at baseline. No safety signals were observed at week 6 post-treatment.

"These initial DB-OTO results provide encouraging early proof-of-concept for the treatment of otoferlin-related hearing loss, as well as proof-of-concept for our gene therapy pipeline to address more common forms of inherited hearing loss and other therapeutic areas," said Dr. Christos Kyratsous, Senior Vice President of Research at Regeneron and Co-Head of Gene Medicines. "The ongoing CHORD trial is our first clinical-stage hearing program, and we are extremely grateful to the investigators and this child's family for undertaking this groundbreaking trial. We remain committed to advancing this research, and hope these results signify a revolutionary potential for children with inherited hearing loss to ultimately benefit from gene therapies like DB-OTO."

DB-OTO was initially co-developed by Regeneron and Decibel Therapeutics, a collaboration that began in 2017 and was extended in 2021. In September 2023, Regeneron acquired Decibel Therapeutics, solidifying this long-term partnership. In addition to the DB-OTO development program, other clinical efforts include AAV.103 for patients with GJB2-related hearing loss and AAV.104 for patients with stereocilin (STRC)-related hearing loss.

DB-OTO for the treatment of otolin-related hearing loss is currently in clinical development, and its safety and efficacy have not been evaluated by any regulatory agency.

Reference: Company's official website