uniQure N.V. (NASDAQ: QURE) has announced the dosing of the first patient in its Phase I/II clinical trial, EPISOD1 (NCT06100276), of AMT-162 for the treatment of amyotrophic lateral sclerosis (ALS) caused by mutations in the superoxide dismutase 1 (SOD1) gene, referred to as SOD1-ALS. This rare, inherited, and progressive motor neuron disease affects a small subset of the ALS population.
The EPISOD1 trial is a multi-center, open-label study being conducted in the United States. It involves three dose-escalating cohorts to assess the safety, tolerability, and exploratory efficacy of AMT-162 in individuals with SOD1-ALS. The trial is currently recruiting participants at four sites in the U.S., with plans to expand to seven more sites by early 2025.
Walid Abi-Saab, M.D., chief medical officer of uniQure, stated, “We are pleased to announce the first patient dosing of AMT-162, our investigational gene therapy for the treatment of SOD1-ALS, a debilitating, degenerative, and fatal disease. We believe our novel AAV-based gene therapy candidate can deliver on the convenience of one-time dosing with the potential for a differentiated efficacy profile that is needed for such a devastating disease.”
Understanding SOD1-ALS and AMT-162
Mutations in the SOD1 gene are implicated in up to 20% of familial ALS cases and approximately 2% of sporadic ALS cases. These mutations result in the production of a misfolded SOD1 protein that aggregates, leading to motor neuron damage and progressive muscle weakness, ultimately affecting the ability to move, speak, swallow, and breathe.
AMT-162, licensed from Apic Bio, is an AAVrh10-based gene therapy that delivers a microRNA designed to reduce the expression of the mutated SOD1 protein. By targeting the messenger RNA that carries instructions for producing SOD1, AMT-162 aims to decrease the amount of misfolded protein, potentially slowing or halting disease progression. The therapy is administered via a one-time intrathecal injection into the spinal canal.
Clinical Trial Design and Endpoints
The EPISOD1 trial aims to enroll approximately 20 adults with a confirmed genetic diagnosis of SOD1-ALS who are experiencing lower motor neuron symptoms, with or without upper motor neuron involvement. Participants will receive a short course of immunosuppression before and after the AMT-162 infusion and will be monitored for up to five years.
The primary endpoint of the study is to assess the safety of the gene therapy, based on the incidence and severity of treatment-related adverse events. Secondary endpoints include evaluating immune responses to AMT-162 and monitoring changes in lung function, muscle strength, and levels of neurofilament light chain (NfL), a biomarker of nerve cell damage.
Regulatory Designations and Future Directions
AMT-162 has been granted both Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA), which provide incentives to accelerate its clinical development. uniQure is also conducting clinical trials for gene therapy candidates targeting Huntington’s disease, temporal lobe epilepsy, and Fabry disease.
“The start of this trial marks the advancement of our third gene therapy program into the clinic with this trial design, continuing our goal of rapidly generating proof-of-concept data using well-established biomarkers in order to bring treatments to patients as quickly as possible,” added Abi-Saab.
