uniQure has dosed the first patient in the phase 1/2 clinical trial of its experimental gene therapy, AMT-162, for the treatment of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase 1 (SOD1), a rare, inherited and progressive motor neuron disease.
EPISOD1 is a multi-center, open-label trial being conducted in the U.S. with three dose-escalating cohorts assessing the safety, tolerability and exploratory signs of efficacy of AMT-162 in individuals with SOD1-ALS. The three cohorts will have up to four patients, each receiving a short course of immunosuppression prior to and after an intrathecal (near the spinal cord) infusion of AMT-162. This is uniQure's third gene therapy program in the clinic with this type of trial design.
There are currently four active trial sites for EPISOD1 in the U.S., and uniQure plans to activate seven additional sites by the first quarter of 2025.
Patients with SOD1-ALS — approximately 2% of the ALS population — express a misfolded SOD1 protein. This misfolded protein is toxic to motor neurons causing degeneration which, over time leads to muscle weakness, loss of function and eventually death. AMT-162 is an investigational AAVrh10-based gene therapy that expresses a miRNA designed to knock down the expression of that mutated SOD1 protein.
According to uniQure, AMT-162 may offer a novel one-time, intrathecally administered approach to slowing or halting the progression of SOD1-ALS.
UniQure has a track record of development success in gene therapy. Back in 2020, the Amsterdam-based drugmaker sold the rights to its novel late-stage gene therapy candidate for hemophilia B to CSL Behring for $450 million. In November 2022, the treatment, branded Hemgenix, became the first FDA-approved gene therapy for adults with Hemophilia B.