The clearance of the CTA is the latest in a series regulatory decisions enabling Decibel Therapeutics’ international clinical development plans.
Decibel Therapeutics’ DB-OTO, an investigational adeno-associated virus (AAV) dual-vector-based gene therapy intended to treat otoferlin-related hearing loss, has received clearance of its clinical trial application (CTA) by the Spanish Agency of Medicines and Medical Devices (AEMPS).1
The clearance of the CTA, which was originally submitted to the AEMPS in November 2022, is the latest in a series regulatory decisions enabling the company’s international clinical development plans for the gene therapy.2 Earlier this year, in January 2023, Decibel received clearance of a CTA for DB-OTO from the United Kingdom’s Medicines and Healthcare products Regulatory Agency.3 Prior to that, in October 2022, the company received clearance of an investigational new drug application for the gene therapy from the FDA.4
Decibel intends to initiate a phase 1/2 dose escalation clinical trial, dubbed CHORD (NCT05788536), which will seek to enroll patients aged 2 years or younger in Spain and the UK.1 The company expects to provide an interim safety and efficacy data readout for the trial in the first quarter of 2024.
“Spain is an important country within our DB-OTO clinical development strategy, and our trial will leverage the collaborations and natural history work that we have pursued there over the past several years,” Laurence Reid, PhD, the CEO of Decibel, said in a statement.1 “Our team believes that DB-OTO could be a transformative treatment for individuals with otoferlin-related hearing loss, and this approval broadens the opportunity to evaluate its potential in infants 2 years of age and younger.”
DB-OTO, which is being developed in collaboration with Regeneron Pharmaceuticals, utilizes a cell-selective promoter to enable expression of otoferlin, the disease-targeted protein, in cochlear inner hair cells.4 Decibel has stated that it will use auditory brainstem response, which was previously utilized to evaluate responses to DB-OTO in preclinical research with animal models, as a measure of efficacy in the CHORD trial.1 Recently, in March 2023, DB-OTO received orphan drug designation (ODD) from the European Medicines Agency (EMA).1 Earlier, in 2021, it was granted both ODD and rare pediatric disease designation by the FDA.
“Decibel has generated compelling preclinical data showing DB-OTO’s potential, and we are on track to initiate CHORD, our global phase 1/2 clinical trial of DB-OTO, in the first half of this year,” Reid said in a statement made at the time DB-OTO received ODD from the EMA.5
Several other companies are also developing gene therapies for otoferlin-related hearing loss. Among these are Sensorion’s OTOF-GT, which is intended to deliver the otoferlin gene via a dual AAV vector for assembly in place, and Akouos's AK-OTOF, which is also an investigational dual AAV vector-based gene therapy intended for the treatment of OTOF-mediated hearing loss.6,7
OTOF-GT has received ODD and rare pediatric disease designation from the FDA and ODD from the European Commission.6,8 At the time it received the ODD from the FDA in November 2022, the company stated that it expected to submit a CTA for OTOF-GT, which remains in the preclinical stage of development, during the first half of 2023.
Meanwhile, AK-OTOF received clearance of its IND application by the FDA in September 2022.9 The FDA granted AK-OTOF ODD and rare pediatric disease designation in 2021. Notably, on December 1, 202, Akuous was acquired by Eli Lilly and Company.10 As of April 20, 2023, a phase 1/2 clinical trial (NCT05821959) evaluating AK-OTOF is recruiting patients aged 2 to 17 years with biallelic mutations in the otoferlin gene and profound bilateral sensorineural hearing loss.
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