Akouos (a wholly owned subsidiary of Eli Lilly and Company) has announced positive initial clinical results from their Phase I/II AK-OTOF-101 gene therapy study. The first participant to receive the gene therapy, an 11-year-old with profound hearing loss from birth, experienced restored hearing within 30 days of AK-OTOF administration.

In this individual (the first to receive gene therapy in the United States for a genetic form of hearing loss) hearing was restored across all tested frequencies (achieving thresholds of 65 to 20 dB HL) and within the normal hearing range at some frequencies at the Day 30 visit. The company noted that both the surgical administration procedure and the investigational therapy were well tolerated, and no serious adverse events were reported.

“Gene therapy for hearing loss is something physicians and scientists around the world have been working toward for over 20 years,” said John Germiller, MD, PhD, attending surgeon and director of clinical research in the division of otolaryngology at Children’s Hospital of Philadelphia, and a principal investigator of the AK-OTOF-101 clinical trial who administered AK-OTOF to this participant. “These initial results show that it may restore hearing better than many thought possible.”

Akouos was co-founded by Manny Simons, PhD, the company’s CEO, in 2016. The company’s two leading programs are the first two inner ear AAV programs to enter clinical development. AK-OTOF is an AAV gene therapy for the restoration of hearing in individuals with a genetic sensorineural hearing loss due to mutations in the otoferlin gene. The otoferlin gene is expressed in the sensory cells that are found in the inner ear and that convert sound-driven fluid waves into neural signals.

To date, there has never been a single drug or biologic approved for direct inner ear administration. The inner ear is not easy to access. It is closer to the brain than the middle ear, and the sensory cells are encased in a fluid-filled, bony structure.

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.

Simons told GEN in 2022 that AAV gene therapies are “ideally suited to the inner ear.” AAV vectors can be delivered directly without exposure to the rest of the body, allowing a high ratio of vector to contact the target cells. Also, the hair cells don’t divide, which means the expression of functional genes may be sustained over the long term.

In the AK-OTOF-101 trial, participants receive a single, unilateral intracochlear administration of AK-OTOF. Participants in cohort 1 receive AK-OTOF at a dose of 4.1E11 total vector genomes.

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.

These results, including initial data from a second participant to receive AK-OTOF, will be presented during the Late Breaking Presidential Symposium at the 2024 Association for Research in Otolaryngology (ARO) MidWinter Meeting.

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PackGene is a CRO & CDMO technology company that specializes in packaging recombinant adeno-associated virus (rAAV) vectors. Since its establishment in 2014, PackGene has been a leader in the AAV vector CRO service field, providing tens of thousands of custom batches of AAV samples to customers in over 20 countries. PackGene offers a one-stop CMC solution for the early development, pre-clinical development, clinical trials, and drug approval of rAAV vector drugs for cell and gene therapy (CGT) companies that is fast, cost-effective, high-quality, and scalable. Additionally, the company provides compliant services for the GMP-scale production of AAVs and plasmids for pharmaceutical companies, utilizing five technology platforms, including the π-Alpha 293 cell AAV high-yield platform and the π-Omega plasmid high-yield platform. PackGene's mission is to make gene therapy affordable and accelerate the launch of innovative gene drugs. The company aims to simplify the challenging aspects of gene therapy development and industrialization processes and provide stable, efficient, and economical rAAV Fast Services to accelerate gene and cell therapy development efforts from discovery phase to commercialization.

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