A single intracochlear dose of an adeno-associated virus (AAV)-based gene therapy resulted in no serious treatment-emergent adverse events and no dose-limiting toxicities in the first four people treated for unilateral vestibular schwannoma, according to initial results from the phase 1/2 AK-antiVEGF-101 trial.
Michael McKenna, MD, presented the findings at the AAO-HNSF 2026 Annual Meeting on behalf of the AK-antiVEGF-101 Trial and Study Site Teams and Eli Lilly and Company.
Background
Vestibular schwannoma is a benign tumor of the vestibulocochlear nerve that causes progressive hearing loss. Surgery and radiation can control the tumor but do not improve hearing. Systemic VEGF inhibition has shown preliminary tumor control and hearing improvement in some patients with neurofibromatosis type 2, but systemic toxicity can limit its use in vestibular schwannoma. The investigational therapy, AAVAnc80-antiVEGF, is designed to produce anti-VEGF protein locally within the tumor microenvironment.
Study Design
AK-antiVEGF-101 (NCT06517888) is an open-label, nonrandomized, dose-escalation phase 1/2 trial in adults with progressive unilateral vestibular schwannoma and profound hearing loss. The trial began enrolling Jan. 17, 2025, and plans call for three sequential single-ascending-dose cohorts and a dose expansion cohort. The main objectives of the trial are to assess the safety and efficacy of the therapy when given by the intracochlear route.
Participants receive a single unilateral intracochlear administration of AAVAnc80-antiVEGF in the study ear via the Akouos Delivery Device, a sterile, single-use investigational device.
Eligible participants are adults with unilateral, progressive vestibular schwannoma larger than 2 mm and profound hearing loss in the affected ear. Exclusion criteria include a prior diagnosis of neurofibromatosis type 2 or bilateral vestibular schwannoma, prior surgery or radiation for the tumor, a clinical history consistent with endolymphatic hydrops, profound hearing loss in the unaffected ear, and prior participation in a gene therapy trial. Participants must also be willing to join a separate long-term follow-up study after the trial ends.
The primary outcome measure is the frequency of adverse events related to the product or the administration procedure, including the device, assessed through trial completion at about one year. Secondary outcomes are change in tumor volume from baseline on volumetric MRI and device performance, measured by the frequency of device deficiencies during delivery.
Initial Safety Data
As of Jan. 29, 2026, four participants (three men and one woman) in Cohort 1 had been treated, with ages 33 to 79. The longest follow-up was through Day 180.
No serious treatment-emergent adverse events were reported. Two Grade 1 non-serious adverse events occurred in two of the four participants. Both were assessed as unrelated to AAVAnc80-antiVEGF, the delivery device or the administration procedure. No dose-limiting toxicities were observed, and no stopping rule criteria were met.
Serum anti-VEGF protein was undetectable at the data cutoff, and no anti-drug antibodies were found in serum. Vector shedding was transient and limited to swabs of the study ear and saliva.
The authors concluded that the initial safety profile supports further evaluation of AAVAnc80-antiVEGF as a potential treatment for progressive vestibular schwannoma. Enrollment in the study continues.
The study is sponsored by Akouos, with Lilly listed as a collaborator. McKenna reported financial relationships with Eli Lilly and Company (employee).
