The company previously presented positive preclinical data at the 2021 ASGCT meeting.
Decibel Therapeutics has submitted an investigational new drug application (IND) to the FDA for its gene therapy candidate DB-OTO for the intended treatment of profound congenital hearing loss due to an otoferlin deficiency in pediatric patients.1
“This submission is an important milestone for the Decibel team as we continue advancing our gene therapy pipeline to address areas of unmet medical need. DB-OTO may potentially provide a new treatment option for children born with otoferlin deficiency, a leading cause of infant hearing loss, for which there are no approved pharmaceutical remedies,” Laurence Reid, PhD, chief executive officer, Decibel, said in a statement.1 “We look forward to initiating a phase 1/2 clinical trial of DB-OTO in pediatric patients in the first half of 2023, pending regulatory clearance.”
DB-OTO, an adeno-associated virus (AAV) dual vector gene therapy, is being developed by Decibel in collaboration with Regeneron Pharmaceuticals. It expresses the otoferlin transgene in hair cells using a proprietary, cell-selective promoter, and is designed to enable the ear to transmit sound and restore hearing. It received orphan drug and rare pediatric disease designations from the FDA in September 2021.2
“We are pleased to receive these important designations from the FDA, which support our conviction that innovative treatments for congenital hearing loss are urgently needed,” Heather Wolff, vice president, clinical development operations, Decibel, said in a statement at that time.2
Prior to that, Decibel presented preclinical data at the 24th Annual Meeting of the American Society of Gene & Cell Therapy in May 2021.3 The data demonstrated DB-OTO's pharmacological modulation of otoferlin expression and durable functional rescue in mice as measured by the Auditory Brainstem Response.
Investigators tested a surgical delivery approach in mice translatable into routine otolaryngological practice to restrict transgene expression and prevent dose-limiting toxicities. The approach uses slow AAV infusion through the round window membrane and vestibular fenestration to allow egress of displaced perilymph by the therapy. This approach will be assessed in a potential clinical trial.
“Of the 1 in 500 neonates who are born with hearing loss annually in the US, 50 to 200 are caused by Otoferlin deficiency. There are no approved therapies for Otoferlin deficiency; infants with biallelic OTOF mutations are currently managed with assistive devices,” first author Adam Palermo, PhD, vice president, molecular platform, Decibel, and colleagues wrote.3 “DB-OTO is a promising emerging therapeutic for genetic hearing loss and has the potential to provide the first clinical proof-of-concept for gene therapy in the inner ear."