Gene therapy improves auditory responses in children with severe genetic hearing loss

contemporary pediatrics® This article was first published. This version has been lightly edited.

Gene therapy improves auditory responses in children with severe genetic hearing loss Image credit: Marija – stock.adobe.com.

Regeneron Pharmaceuticals recently announced improved audit response after a child with severe genetic hearing loss became the first patient to receive investigational Otoferlin gene therapy (DB-OTO) in the Phase 1/2 CHORD clinical trial.

In the CHORD trial (NCT05788536), the child less than 2 years of age received an intracochlear injection of DB-OTO into one ear. Regeneron said in a press release on October 26, 2023 that during planned follow-up, observations were made “compared to baseline at Week 6 based on auditory brainstem response (ABR) and behavioral (pure tone) audiometry.” Auditory response improved.

ABR is a clinically accepted physiological measure of hearing sensitivity. As of the trial baseline visit, the child had no hearing sensitivity in either ear. No relevant safety signals were observed at week 6 of treatment.

Manohar Bance, MB, an ear surgeon at the University of Cambridge and lead trial investigator, said: “Children who participate in CHORD often have profound hearing loss due to mutations in a single gene, Otoferlin, which essentially shuts down their hearing loss. Auditory circuitry.” NHS Foundation Trust, in a press release. “Cochlear implants are the current standard of care, but cannot replicate the full complexity and range of sound. With these very preliminary DB-OTO results, we now have encouraging evidence that this gene therapy may be able to help regenerate Opening up these audit loops. “We look forward to further following this child and others to determine whether DB-OTO gene therapy can restore clinically meaningful hearing as they learn to interact with the world. “

Currently, there are no approved medical treatments for congenital hearing loss, which affects approximately 1.7 out of 1,000 children born in the United States. Hearing loss caused by mutations in the otoferrin gene is extremely rare. Although uncommon, most cases of permanent congenital hearing loss diagnosed in developed countries are sensorineural and caused by defects in a single gene, making gene therapy a potential treatment option.

1/2 The CHORD trial is a first-in-human, open-label, multicenter trial designed to evaluate the safety, tolerability and preliminary efficacy of DB-OTO in pediatric patients (under 18 years of age) with Otoferlin mutations.

The trial, which is currently recruiting children across the US, UK and Spain, is divided into two parts. Part A is the initial dose-escalation cohort, in which patients receive a single injection in one ear. In Part B (expansion cohort), enrolled individuals will receive a single injection in both ears at the dose selected in Part A.

The gene therapy is an investigational cell-selective adeno-associated viral gene therapy designed to provide hearing for patients with severe congenital hearing loss caused by mutations in the otoferlin gene. The purpose of DB-OTO is to “use a modified, non-pathogenic virus to deliver a working copy of the defective otoferlin gene by injection into the cochlea under general anesthesia, a procedure similar to that used in cochlear implants,” Regeneron said.

The introduced otoferlin gene is under the control of a proprietary cell-specific Myo15 prompt, which is designed to restrict expression only to cells that normally express otoferlin. The gene therapy received Orphan Drug and Rare Pediatric Disease designations from the FDA in 2021.

Regeneron noted that the potential use of DB-OTO has not yet been evaluated by any regulatory agency.

refer to

Preliminary results shared by Regeneron show that gene therapy improves auditory responses in children with severe genetic hearing loss. Press Releases. Regeneron Pharmaceuticals. October 26, 2023. Accessed 31 October 2023. https://tinyurl.com/57e27sey