According to the American Hearing Research Foundation, about one out of every 1,000 to 2,000 births involves congenital deafness.[1] There are approximately 150 genes linked to sensorineural hearing loss.[2]
Approximately 200,000 people worldwide are deaf due to a mutation in the otoferlin (OTOF) gene.[3] The first gene therapy in clinical studies is a dual adeno-associated viral (AAV) vector-based gene therapy which seeks to replace the nonfunctioning OTOF gene in the cochlea with a working copy of the OTOF gene and is currently being evaluated in the phase 1/2 AK-OTOF-101 clinical trial (NCT05821959). [4], [5]
According to the Children’s Hospital of Philadelphia,
Gene therapy for children with OTOF gene-related deafness seeks to restore hearing by injecting copies of normal OTOF genes into the inner ear. With normal OTOF genes, the sensory cells will be able to function so they can respond to sound and activate the auditory nerve to send impulses to the brain. Functioning OTOF genes are encased in a viral vector, a modified form of a non-disease-causing virus, so they can be delivered into cochlear cells in the inner ear.
Because the cochlea is encased on a bony chamber that is difficult to reach, the gene therapy is delivered to the inner ear using a special device, in a minimally invasive surgical procedure developed at Children’s Hospital of Philadelphia. The gene therapy is placed into the inner ear using a device called an endoscope that lifts up the ear drum, allowing a special probe to reach the “round window,” a tiny area that leads to the cochlea. A single, very small dose of normal OTOF genes is then delivered to the inner ear.
After the procedure, which requires an overnight stay in the hospital, children are monitored for two years for any side effects. The aim is for the normal OTOF genes to function in the cochlea and replace the faulty genes, restoring a child’s hearing.
The clinical study, AK-OTOF-101, is sponsored by Akouos, Inc., a wholly owned subsidiary of Eli Lilly and Company. According to Lilly’s press release on January 23, 2024: “The first participant to receive AK-OTOF in the study, an 11-year-old at the time of AK-OTOF administration with profound hearing loss from birth, experienced restored hearing within 30 days of AK-OTOF administration. In this individual, hearing was restored across all tested frequencies, achieving thresholds of 65 to 20 dB HL, and within the normal hearing range at some frequencies at the Day 30 visit. Both the surgical administration procedure and the investigational therapy were well tolerated, and no serious adverse events were reported.”[6]
In the United States, there are two locations currently recruiting for clinical trial AK-OTOF-101, University of Iowa, Iowa City, and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. To be eligible, children need to be between ages 2-17, with biallelic mutations in the otoferlin gene, and cannot have cochlear implants. Additional eligibility criteria and contact information may be found at https://clinicaltrials.gov/study/NCT05821959?locStr=Philadelphia,%20PA&country=United%20States&state=Pennsylvania&city=Philadelphia&cond=Deafness&rank=7.[7]
Article by Kathy Clark, RN, BSN, CMCN, Vice President, Director of Managed Care. For more information about how this may affect your plan, please contact your Summit ReSources care specialist. The following sources were used as reference material for this article:
[1] Department of Otolaryngology. Blog: Is Deafness Inherited. Accessed 02/16/2024. https://www.ent.uci.edu/learning-center/blog/is-deafness-inherited.asp#:~:text=According%20to%20the%20American%20Hearing,75%25%20of%20congenital%20deafness%20cases.
[2] Childrens Hospital of Philadelphia. Gene Therapy for Genetic Hearing Loss. Accessed 02/16/2024. https://www.chop.edu/treatments/gene-therapy-genetic-hearing-loss
[3] Harvard Medical School. Experimental Gene Therapy Enables Hearing in Five Children Born Deaf. Accessed 02/16/2024. https://hms.harvard.edu/news/experimental-gene-therapy-enables-hearing-five-children-born-deaf
[4] Childrens Hospital of Philadelphia. Gene Therapy for Genetic Hearing Loss. Accessed 02/16/2024. https://www.chop.edu/treatments/gene-therapy-genetic-hearing-loss
[5] CGT Live. Akouos Seeks to Tackle Otoferlin Gene-Mediated Hearing Loss With Phase 1/2 Clinical Trial and Associated Natural History Study. Accessed 2/16/2024. https://www.cgtlive.com/view/akouos-seeks-tackle-otoferlin-gene-mediated-hearing-loss-phase-clinical-trial-associated-natural-history-study
[6] Lilly Investors. News Release: Positive Phase 1/2 Clinical Trial Data for an Investigational Gene Therapy for Genetic Hearing Loss to be Presented at the Association for Research in Otolaryngology 2024 MidWinter Meeting. Accessed 2/16/2024. https://investor.lilly.com/news-releases/news-release-details/positive-phase-12-clinical-trial-data-investigational-gene
[7] ClinicalTrials.Gov. Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss. Accessed 2/16/2024. https://clinicaltrials.gov/study/NCT05821959?locStr=Philadelphia,%20PA&country=United%20States&state=Pennsylvania&city=Philadelphia&cond=Deafness&rank=7