BOSTON, MASSACHUSSETTS — Akouos, Inc. (NASDAQ: AKUS), a precision genetic medicine company dedicated to developing potential gene therapies for individuals living with disabling hearing loss worldwide, announced that it has received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application to initiate a Phase 1/2, first in human, pediatric clinical trial of AK-OTOF, a gene therapy intended for the treatment of patients with otoferlin gene (OTOF)-mediated hearing loss.
Currently, there are no approved pharmacologic treatment options for individuals with OTOF-mediated hearing loss, a form of sensorineural hearing loss caused by mutations in the OTOF gene.
“The AK-OTOF IND clearance from FDA is an important step toward achieving our mission of making healthy hearing available to all. This first in human clinical trial for AK-OTOF is groundbreaking and highlights Akouos’s leadership in the field — we expect this to be the first clinical trial for a genetic inner ear condition, the first in which an AAV gene therapy is administered to the inner ear, and the first for any inner ear condition to begin in a pediatric population.”
–Manny Simons, Ph.D., M.B.A., Co-Founder, President and CEO of Akouos
“We are excited to advance AK-OTOF into clinical development. There is a significant unmet need in OTOF-mediated hearing loss, as individuals typically have Severe to Profound sensorineural hearing loss from birth, and there are currently no approved pharmacologic options,” said Jen Wellman, chief operating officer of Akouos. “This clinical trial is designed not only to evaluate the safety and potential benefit of AK-OTOF for individuals with OTOF-mediated hearing loss, but also to help us demonstrate the applicability of our novel delivery approach to a broad range of inner ear conditions. We look forward to sharing what we learn from this pioneering work.”
OTOF-mediated hearing loss is a form of sensorineural hearing loss caused by mutations in the otoferlin gene, which encodes otoferlin, a protein that enables the inner hair cells of the cochlea to release neurotransmitter vesicles in response to stimulation by sound to activate auditory neurons. Individuals with OTOF-mediated hearing loss have bilateral hearing loss that is typically Severe to Profound and congenital, exhibiting absent or highly abnormal auditory brainstem response (ABR) from birth. Approximately 20,000 individuals are affected in the United States and Europe.
In April 2021, FDA granted both Orphan Drug Designation and Rare Pediatric Disease Designation for AK-OTOF.
AK-OTOF Gene Therapy
AK-OTOF is a dual adeno-associated viral (AAV) vector-based gene therapy intended to treat patients with OTOF-mediated hearing loss by delivering transgenes encoding OTOF to the inner hair cells (IHCs) of the cochlea.
A one-time, unilateral intracochlear administration of AK-OTOF is intended to result in the expression of normal full-length functional otoferlin protein in the IHCs, which has the potential to lead to recovery of auditory function.
The advancement of AK-OTOF into clinical development is supported by nonclinical data demonstrating administration of AK-OTOF in Otof knockout mice results in durable expression of human otoferlin protein sufficient for sustained restoration of auditory function, as assessed by translationally relevant ABR assessments. In both mice and non-human primates, AK-OTOF was systemically and locally well tolerated, and no adverse effects were observed in clinical pathology, otic pathology, systemic histopathology, or auditory or cochlear function.
The Phase 1/2 clinical trial is designed to evaluate the safety and tolerability of escalating doses of AK-OTOF administered unilaterally to trial participants with OTOF-mediated hearing loss; it is also designed to assess efficacy through clinical measures such as ABR, which is an objective, clinically accepted endpoint. Given both the early onset of serious manifestations, as well as the need for timely intervention due to anatomical considerations and developmental considerations, eligible participants for the clinical trial will be pediatric. Based on interactions with FDA during the 30-day IND review period, the Company expects the first two participants will be as young as seven years of age, and that subsequent participants will be as young as two years of age at the time of administration.
The company plans to provide an update on clinical trial initiation activities for AK-OTOF later this year.
Akouos is a precision genetic medicine company dedicated to developing gene therapies with the potential to restore, improve, and preserve high-acuity physiologic hearing for individuals living with disabling hearing loss worldwide. Leveraging its precision genetic medicine platform that incorporates a proprietary adeno-associated viral (AAV) vector library and a novel delivery approach, Akouos is focused on developing precision therapies for forms of sensorineural hearing loss. Headquartered in Boston, Akouos was founded in 2016 by leaders in the fields of neurotology, genetics, inner ear drug delivery, and AAV gene therapy.