By Nancy M. Williams
Gene therapy has transformed hearing for seven profoundly deaf children with variants of a gene called otoferlin, in three investigational trials around the globe (as of late February 2024).
I have been involved with hearing restoration for over a decade, starting with my board role with Hearing Health Foundation and now as the founder of Auditory Insight, a strategy firm focused exclusively on hearing healthcare through which I have advised gene therapy companies. I am also a person with a genetic, progressive hearing loss.
Given my roles, I am pleased to report that early results from these trials fared well in our rigorous analysis. They provide the first validation of pharmacological treatments for hearing loss.
Our independent analysis of the clinical trials’ published data yields the following insights on gene therapy for hearing loss from otoferlin variants.
Credit: Auditory Insight
Target Population
The gene therapy partially restored hearing in children with otoferlin variants ranging in age from 10 months to 11 years. The 11-year-old boy gaining hearing is particularly of note, since he had lived over a decade without sound stimulating his brain.
Time to Results
The gene expression has a time-release pattern, with patients showing an improvement in hearing over time and the time to full results at least 26 weeks.
Although patients experience significant improvements in hearing as early as four weeks, the subjects of the Refreshgene Therapeutics trial were still showing hearing gains at 26 weeks. So, the time to full results appears to be at least six months. The Refreshgene trial investigators noted in The Lancet that they will continue to follow up with patients to understand the “temporal pattern.”
Efficacy
To date, all three of the trials appear to have restored hearing in the treated ear from profoundly deaf to moderate (or moderately-severe in one case). Hearing levels transformed from an inability to hear a shouted voice in the ear to difficulty only hearing a soft voice three feet away (or a normal voice for moderately- severe). Efficacy may continue to improve over time.
Device Indications
The experimental gene therapy has transformed device indications for the treated ears to hearing aids instead of cochlear implants. Restoring hearing to the point where only a hearing aid is needed has tremendous benefits. Hearing outcomes with hearing aids are usually better than with cochlear implants, particularly with the patient’s ability to hear in noisy places, appreciate music’s qualities, and locate the origins of sounds.
These are our four key observations about the clinical trial data to date for the seven patients who achieved positive results. Please click here to read the full analysis.
Nancy M. Williams is the former member of Hearing Health Foundation’s Board of Directors. She is the president and founder of Auditory Insight as well as an accomplished pianist. For more, see Auditory Insight.
Read more about the gene therapy trials as presented at ARO 2024 here.
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I currently work with a mouse model with hearing fluctuation and have a clinical protocol that is performing deep phenotyping of patients with hearing instability, including patients with Ménière’s disease.