INDIANAPOLIS, INDIANA — Akouos, Inc., a wholly owned subsidiary of Eli Lilly and Company (NYSE: LLY), announced positive initial clinical results from the Phase 1/2 AK-OTOF-101 study, which demonstrated restored hearing within 30 days of AK-OTOF administration in the first participant, an individual with over a decade of profound hearing loss.
Results, including initial data from a second participant who received AK-OTOF, will be presented during the Late Breaking Presidential Symposium at the 2024 Association for Research in Otolaryngology (ARO) MidWinter Meeting.
Details of the presentation are:
- Title: Clinical development of AK-OTOF gene therapy for OTOF-mediated hearing loss
Session: Late Breaking Presidential Symposium
Date/Time: Saturday, February 3, 10:00 a.m. PT
Location: Anaheim Marriott, Anaheim, California
The first participant to receive AK-OTOF in the study, an 11-year-old at the time of administration with profound hearing loss from birth, experienced restored hearing within 30 days. Hearing was restored across 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 administration procedure and the investigational therapy were well tolerated, with no serious adverse events reported.
“Gene therapy for hearing loss is something physicians and scientists have been working toward for over 20 years,” said Professor John Germiller, M.D., Ph.D., attending surgeon and Director of Clinical Research in the Division of Otolaryngology at Children’s Hospital of Philadelphia, and a principal investigator who administered AK-OTOF. “These initial results show it may restore hearing better than many thought possible.”
Gene Therapy Treatment for Hearing Loss
In the AK-OTOF-101 trial, eligible participants receive a single, unilateral intracochlear administration of AK-OTOF, with hearing restoration assessed by audiometry and auditory brainstem response (ABR). Participants in cohort 1 receive AK-OTOF at 4.1E11 total vector genomes.
“Children with OTOF-mediated hearing loss often have profound loss from birth, yet only a fraction have genetic testing to receive a definitive diagnosis,” said Dr. Oliver Haag, pediatric otolaryngologist and Head of Otolaryngology at Sant Joan de Deu Hospital in Barcelona, and an investigator in Akouos’s AK-OTOF-NHS-002 Natural History Study.
“This trial and study show the power of international collaboration for rare genetic conditions. It is gratifying to see this effort benefit the first participant.”
Hearing loss is the most common sensory condition. With no approved drugs to restore hearing, it represents significant unmet need. Delivering a healthy gene to target cells in the inner ear has potential to enable hearing for some cases, including an estimated 200,000 with OTOF-mediated loss. OTOF-mediated loss is the first monogenic form investigated in a gene therapy trial.
“We are grateful to the participants, families, investigators and collaborators working together on this pioneering trial,” said Emmanuel Simons, Ph.D., M.B.A., CEO of Akouos and SVP, Gene Therapy at Lilly. “These initial results highlight the potential impact genetic medicines could have and reinforce our mission to make healthy hearing available to all.”
AK-OTOF has been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the FDA and a positive opinion on orphan designation by the European Medicines Agency.
About AK-OTOF and the AK-OTOF-101 Clinical Trial
AK-OTOF (AAVAnc80-hOTOF) is a dual adeno-associated viral (AAV) vector-based gene therapy designed to restore auditory function by gene transfer and durable expression of normal, functional otoferlin protein to the inner hair cells of the cochlea. AK-OTOF utilizes AAVAnc80, a capsid with high transduction efficiency for inner hair cells, together with a strong ubiquitous promoter to achieve expression of otoferlin, observed only in the target inner hair cells, at levels that have the potential to restore high acuity physiologic hearing. The Akouos delivery device, being developed in parallel specifically for intracochlear administration, enables a minimally invasive surgical approach to deliver AK-OTOF throughout the cochlea. The AK-OTOF-101 Clinical Trial (NCT05821959) is a Phase 1/2 trial that is assessing the safety, tolerability, and bioactivity of escalating doses of AK-OTOF delivered via the Akouos delivery device. More information about the trial can be found at https://www.clinicaltrials.gov/study/NCT05821959.
About the OTOF-mediated Hearing Loss Natural History Study
The AK-OTOF-NHS-002 Natural History Study (NCT05572073) is designed to characterize the natural history of OTOF-mediated hearing loss, including progression of physiologic responses and audiologic outcomes over time, potential genotype-phenotype relationships, and longitudinal assessment of clinical outcomes. More information about the study can be found at https://www.clinicaltrials.gov/ct2/show/NCT05572073.
About Lilly
Lilly unites caring with discovery to create medicines that make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer’s disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable.
Source: Eli Lilly
