AK-OTOF shows early hearing restoration potential in children with OTOF-mediated hearing loss

Gene therapy for inherited hearing loss continues to advance, with new preliminary findings from the phase 1/2 AK-OTOF-101 clinical trial suggesting the investigational therapy AK-OTOF may restore functional hearing in children with OTOF-mediated sensorineural hearing loss.

Presented at the Combined Otolaryngology Spring Meetings, the data represent the largest disclosure from the AK-OTOF program to date and include early bilateral administration results in 18 participants across 2 dose levels. According to Akouos, a wholly owned subsidiary of Eli Lilly and Company, 80% of participants who received the higher dose achieved hearing improvement to at least a moderate hearing loss level, with auditory responses observed as early as 30 days after treatment.

In this Q&A, Eliot Shearer, MD, PhD, of Boston Children;s Hospital and principal investigator of the AK-OTOF-101 trial, discusses the clinical implications of these early findings for pediatric hearing loss care. Shearer explains how rapid auditory brainstem response activation and behavioral hearing improvements may influence speech and language development, outlines safety considerations surrounding cochlear gene therapy delivery in young children, and discusses how therapies such as AK-OTOF could eventually fit into evolving pediatric hearing loss management pathways.

Contemporary Pediatrics: The study reports that 80% of participants receiving the higher dose achieved hearing improvement to at least a moderate hearing loss level. How clinically meaningful is this degree of improvement for pediatric patients in terms of language development and daily functioning?

Eliot Shearer, MD, PhD: Hearing is more than sound; it’s the cornerstone of how children connect, learn language, and develop. For children born with OTOF-mediated hearing loss, those opportunities have been out of reach, which is why these preliminary data are so encouraging.

Among participants who received the higher dose of AK-OTOF, 8 out of 10 children showed PTA [pure tone average)–4 improvement, a key measure of functional hearing that is the average of pure tone thresholds at 4 core frequencies crucial for understanding human speech. These children went from having severe to profound hearing loss to a level where many sounds, including speech, became accessible. Previously, the only option for these children to attain these hearing levels would be cochlear implants, which don’t restore natural, 24/7 hearing.

It’s important to note that these data are early and the trial is ongoing. But the improvements we’re observing reinforce our belief in AK-OTOF’s potential to make a meaningful difference in impacted children’s lives.

Contemporary Pediatrics: Functional hearing improvements and auditory brainstem responses were observed as early as 30 days after administration. How should pediatricians interpret this early onset of effect when counseling families about expected timelines?

Shearer:

The study results showing auditory brainstem responses and functional hearing improvements being observed as early as 30 days after administration are significant for the pediatric community because they provide early evidence of functional auditory pathway activation.

When counseling families, it is helpful to frame these milestones as early signs of efficacy rather than a guarantee that every child will experience the same degree of response or follow the same timeline. Because this is an investigational therapy and the trial is ongoing, it is important for pediatricians to set realistic expectations. They can emphasize that individual responses may vary and that consistent, careful follow-up remains essential to understanding how hearing evolves over time following administration. We expect that hearing provided by AK-OTOF gene therapy will provide access to the full spectrum of sound 24/7. Future studies will be focused on assessing how this affects the acquisition of speech and language in children.

Contemporary Pediatrics: Given the presence of click auditory brainstem responses shortly after treatment, what does this suggest about the restoration of auditory pathway function, and how might this influence long-term auditory outcomes?

Shearer: The presence of click auditory brainstem responses (ABRs) as early as 30 days following administration is highly encouraging because ABR is an objective hearing test that measures how the auditory nerve responds to sound. It doesn’t require the patient to actively participate, which is notable for very young children or those who cannot verbally report hearing sounds.

What we cannot say yet is exactly how those early physiological findings will translate into long-term auditory outcomes across the patient population, which is a primary focus of the ongoing study.

That said, the preliminary data are reassuring. Across those participants we’ve been tracking, hearing improvements have generally remained stable or continued to improve over time. The trial’s earliest participants have been followed for up to 2 years. There is also a long-term follow-up study in which all participants will be monitored for an additional 4 years (approximately), which will be key for assessing the durability and long-term impact of these results.

Contemporary Pediatrics: The therapy was reported to be generally well tolerated with no serious adverse events related to treatment or delivery. What safety considerations should pediatricians keep in mind when evaluating gene therapy options for children with hearing loss?

Shearer: Correct, the study showed that AK-OTOF was generally well tolerated, and there were no serious adverse events related to the gene therapy, the delivery device, or the administration procedure. There were no adverse events of any severity related to the gene therapy or the delivery device.

For young children and infants who may be treated with AK-OTOF, how the therapy is delivered matters, given the delicate anatomical structure of the cochlea. It is important that we preserve the function of the cochlea in order to restore hearing. AK-OTOF is administered via a patent-pending, single-use device designed to deliver the therapy directly and precisely throughout the cochlea, an approach that is intended to be less invasive. And crucially for a pediatric population, the procedure does not require skin incisions or drilling through bone to access the cochlea. Subjects have minimal pain after the procedure. Results from the AK-OTOF trial show no serious adverse events related to administration of the gene therapy, which is highly encouraging. This is likely because we are delivering a very small amount of gene therapy in a localized fashion to the cochlea.

Contemporary Pediatrics: From a practical standpoint, how do you envision AK-OTOF fitting into current pediatric hearing loss management pathways, particularly in relation to early screening, cochlear implantation, or other interventions?

Shearer: If AK-OTOF continues to demonstrate a favorable profile in ongoing studies, I anticipate it will be considered as an option for treatment for children diagnosed with OTOF-mediated hearing loss. Exactly where it fits relative to cochlear implantation and other interventions will depend on the evolving evidence base, the timing of diagnosis, the child’s clinical presentation, and, ultimately, the label if the therapy is approved by regulators.

Early diagnosis through genetic testing will be critical, as identifying the genetic cause of a child’s hearing loss opens the door to a variety of targeted treatment options, including gene therapy.

Reference

Akouos presents preliminary phase 1/2 data for AK-OTOF gene therapy in OTOF-mediated hearing loss at COSM 2026. News release. Eli Lilly and Company. May 11 2026. Accessed May 11, 2026.