Genetic Hearing Loss Gene Therapy: Positive Phase 1/2 Trial Results at 2024 ARO MidWinter

In a groundbreaking development, a gene therapy known as AK-OTOF has shown promising results in restoring hearing in individuals with sensorineural hearing loss caused by mutations in the otoferlin gene (OTOF). The therapy, developed by Akouos, Inc., a subsidiary of Eli Lilly and Company, has demonstrated the ability to restore hearing within a month of a single administration in the first participant of the AK-OTOF-101 study. This individual, who had been profoundly deaf since birth, experienced a significant improvement in hearing across all tested frequencies, reaching thresholds within the normal hearing range.

The therapy involves a single, unilateral intracochlear administration and is assessed through behavioral audiometry and auditory brainstem response (ABR), a standard and objective measure of hearing sensitivity. The first cohort of participants received a dose of 4.1E11 total vector genomes. The procedure and therapy were well-tolerated, with no serious adverse events reported, marking a significant milestone in the field of genetic medicine.

The success of this trial is a testament to the power of international collaboration in developing treatments for rare genetic conditions. It highlights the potential of gene therapy to address a significant unmet need in medicine, as hearing loss is the most common sensory condition and currently lacks approved pharmacological treatments to restore hearing. Millions of people worldwide suffer from disabling hearing loss due to genetic mutations that result in the production of incorrect or incomplete proteins essential for hearing. For conditions like OTOF-mediated hearing loss, which affects an estimated 200,000 individuals globally, gene therapy offers hope by delivering a healthy gene version to target cells within the inner ear, potentially restoring auditory function.

AK-OTOF has been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the FDA and has received a positive opinion on orphan drug designation by the EMA Committee for Orphan Medicinal Products. The clinical trial (NCT05821959) is a Phase 1/2 study assessing the safety, tolerability, and bioactivity of AK-OTOF, while the AK-OTOF-NHS-002 Natural History Study (NCT05572073) aims to characterize the progression of OTOF-mediated hearing loss and related outcomes.

Eli Lilly and Company, with nearly 150 years of pioneering life-changing discoveries, is committed to advancing new treatments for significant health challenges. Their mission to improve life for millions includes making innovative clinical trials accessible and ensuring medicines are affordable. The initial positive results from the AK-OTOF study underscore the potential of genetic medicine to transform the lives of those with OTOF-mediated hearing loss and bring the prospect of restoring hearing within reach.