World Hearing Day 2025: Looking Back at Progress in Gene Therapy
In observance of World Hearing Day, held annually on March 3, CGTLive® took a look back at the past year's news and expert insights in gene therapy for hearing loss indications.
According to the World Health Organization (WHO), disabling hearing loss is defined as hearing loss greater than 35 decibels (dB) in a person's best hearing ear. The organization notes that more than 5% of people across the globe, or 430 million people, need some type of treatment for disabling hearing loss. Of course, the potential causes of hearing loss are quite diverse, but one area of interest for therapeutic development as of late has been congenital hearing loss. Notably, several companies are currently developing gene therapy treatments for otoferlin gene (OTOF)-related hearing loss. Usher syndrome, which includes hearing loss symptoms, is another notable area of activity for gene therapy development.
In honor of World Hearing Day, an event held annually on March 3 that is recognized by WHO, CGTLive® is taking a look back at some of our coverage of gene therapy approaches in hearing loss over the past year. Click the "READ MORE" buttons for more details and information about each item.
Regeneron’s Gene Therapy DB-OTO Improves Hearing in Children With Otoferlin-Related Hearing Loss
February 27, 2025 — Regeneron’s DB-OTO, an investigational adeno-associated virus (AAV) dual-vector-based gene therapy intended to treat OTOF-related hearing loss, has improved hearing in pediatric patients treated in the phase 1/2 CHORD clinical trial (NCT05788536).
The company presented the findings orally at the Association for Research in Otolaryngology’s (ARO) 48th Annual MidWinter Meeting, held February 22 to 26, 2025, in Orlando, Florida. Notably, out of the 11 treated children who had at least 1 posttreatment assessment, 10 showed improved hearing at various decibel hearing levels (dBHL). Furthermore, 1 of the 5 children who had reached their 24-week assessment showed an improvement in average hearing threshold to “nearly normal” hearing levels (≤40 dBHL) and 2 of the 5 children showed an improvement to normal hearing levels (≤25 dBHL). Regeneron noted that 1 of the 11 children who reached the 24-week assessment did not show any change in in hearing from baseline.
Another participant, not included in the aforementioned group of 11 patients, had a 48-weeks posttreatment assessment in which improvement to hearing thresholds within normal limits (0.25-2.0 kHz) in most speech-relevant frequencies were observed. According to Regeneron, positive auditory brainstem responses (ABRs) corroborated the findings. In addition, at 72 weeks posttreatment, this patient showed improvement from 48 weeks posttreatment on formal speech perception tests, with correct identification of words that were presented without visual cues reported.
Sensorion Makes Progress in Trial for OTOF Hearing Loss Gene Therapy
February 21, 2025 — Sensorion’s phase 1/2 AUDIOGENE clinical trial (NCT06370351), which is evaluating investigational AAV vector-based gene therapy SENS-501 (also known as OTOF-GT) for the treatment of OTOF gene-mediated hearing loss, has received clearance from its data monitoring committee (DMC) to move onto dosing its second dose cohort.
The DMC reviewed safety data from the trial’s first cohort, which included 3 patients, and deemed the findings favorable. As such, it has recommended that Sensorion proceed with dosing the second cohort, which will utilize a higher dose and include 3 additional patients. The trial is open to children aged 6 to 31 months and involves intracochlear administration of SENS-501. The administration method was characterized as “well-tolerated” in the first cohort.
Sensorion expects that recruitment of patients for the second cohort will be complete before the midway point of this year. Pending the results of the second cohort, a dose will be selected from the 2 doses evaluated and the trial will move onto an expansion cohort at this dose.
Gene and Cell Therapy Approaches Hold Promise for Usher Syndrome
September 21, 2024 — Zheng-Yi Chen, DPhil, associate scientist, Eaton-Peabody Laboratories, Mass Eye and Ear, and associate professor, Otolaryngology–Head and Neck Surgery, Harvard Medical School, and his colleagues are currently conducting preclinical research that may ultimately contribute to the development of a novel gene editing treatment for Usher syndrome, a rare disease with great unmet need. CGTLive® reached out to Chen to learn more.
Chen gave some background information about the disease itself and the current state of care for patients. He also discussed his lab's own research and pointed out other ongoing research projects at other institutions. He concluded with an optimistic message for the community.
Akouos Seeks to Tackle Otoferlin Gene-Mediated Hearing Loss With Phase 1/2 Clinical Trial and Associated Natural History Study
February 5, 2024 — Eli Lilly and Company subsidiary Akouos’ AK-OTOF (AAVAnc80-hOTOF), an investigational dual AAV vector-based gene therapy intended for the treatment of OTOF-mediated hearing loss, is currently being evaluated in the phase 1/2 AK-OTOF-101 clinical trial (NCT05821959). AK-OTOF delivers transgenes encoding functional OTOF to the inner hair cells of the cochlea via a single unilateral intracochlear administration.
The AK-OTOF-101 study, which was initiated on September 15, 2023, is led by study director Kathy Reape, MD, the chief medical officer of Akouos. The trial has a dose escalation design, and seeks to enroll an estimated 14 participants in total. The participants will receive AK-OTOF at either a low dose level (4.1x1011 total vg/cochlea; DL1) or a high dose level (8.1x1011 total vg/cochlea; DL2). Furthermore, participants will be assigned to 1 of several cohorts. Cohort 1a will include patients aged 7 to 17 years and will treat them at DL1. Cohort 1b will include patients aged 2 to 17 years and will treat them at DL1. Cohort 2 will include patients aged 2 to 17 years and will treat them at DL2.
The trial has an estimated completion date of October 2028. Notably, AK-OTOF will be administered to patients in the trial via an investigational one-time use, sterile medical device, referred to as the Akouos Delivery Device.
