Lawrence R. Lustig, MD, on Evaluating Gene Therapy for the Treatment of Otoferlin-Related Hearing Loss
The chair of the Department of Otolaryngology—Head and Neck Surgery at Columbia University College of Physicians discussed the phase 1/2 CHORD clinical trial evaluating DB-OTO.
“This is going to be big for the field. Now that we have a treatment for genetic deafness, our hope is that this will spur universal genetic testing in all kids with hearing loss, which will give us a much better overview of the genetic landscape of hearing loss in the world. Right now, we know there's a few genes that when they're mutated will lead to deafness, but there's many others for which it's not so clear.”
Decibel Therapeutics and Regenerons’ DB-OTO, an investigational adeno-associated virus (AAV) dual-vector-based gene therapy intended to treat otoferlin-related hearing loss, is currently being evaluated in a first-in-human phase 1/2 dose escalation clinical trial for pediatric patients, referred to by the name CHORD (NCT05788536).1 DB-OTO utilizes a cell-selective promoter to enable expression of otoferlin, the disease-targeted protein, in cochlear inner hair cells. Notably, early results from the first 2 patientstreated in CHORD were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD. Shortly after the presentation, CGTLive® sat down with Lawrence R. Lustig, MD, the chair of the Department of Otolaryngology—Head and Neck Surgery at Columbia University College of Physicians, who presented the data, to learn more.
Lustig went over the key results he presented, noting that adverse events were mostly minor and unrelated to DB-OTO itself. In terms of efficacy, he highlighted that the first child dosed showed essentially normal auditory thresholds at 6 months posttreatment. Furthermore, he pointed out that the second child dosed only has 6 weeks of follow-up, but that based on hearing improvements observed so far he expects that more improvement will occur in this patient over time. Lustig also spoke about how he expects early success with hearing loss gene therapy will impact the field of hearing loss treatment and spoke about overcoming the challenge of delivering the relatively large otoferlin gene with the dual AAV vector.
REFERENCES
1. Lustig L, Bance M, Ishiyama A, et al. Intracochlear administration of DB-OTO gene therapy in pediatric patients with profound hearing loss due to otoferlin mutations: the CHORD phase 1/2 open-label trial. Presented at: ASGCT Annual Meeting 2024, May 7-10; Baltimore, Maryland. Abstract #10.
2. Decibel therapeutics receives FDA clearance of IND application for DB-OTO, a gene therapy product candidate designed to provide hearing to individuals with otoferlin-related hearing loss. News release. Decibel Therapeutics. October 17, 2022.
https://ir.decibeltx.com/news-releases/news-release-details/decibel-therapeutics-receives-fda-clearance-ind-application-db
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