uniQure's AMT-162 Gene Therapy for SOD1-ALS Advances to Second Dose Cohort

• uniQure's AMT-162, a gene therapy for SOD1-ALS, has received the green light from the IDMC to proceed with enrollment in the second dose cohort of its Phase I/II EPISOD1 trial.
• The decision follows a review of safety data from the first cohort, which showed no significant safety concerns, marking a positive step in the therapy's clinical development.
• AMT-162 utilizes an AAVrh10 vector to deliver a microRNA designed to silence the mutated SOD1 gene, offering a potential one-time treatment for this rare form of ALS.
• The EPISOD1 trial is ongoing in multiple centers across the U.S. and is evaluating the safety, tolerability, and preliminary efficacy of AMT-162 in SOD1-ALS patients.

uniQure has announced that the Independent Data Monitoring Committee (IDMC) has recommended proceeding with enrollment in the second dose cohort of the Phase I/II EPISOD1 clinical trial for AMT-162, a gene therapy targeting amyotrophic lateral sclerosis (ALS) caused by mutations in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS). The decision follows a review of 28-day post-treatment data from the first cohort, which revealed no significant safety concerns.

Advancing AMT-162 for SOD1-ALS

AMT-162 is an investigational adeno-associated virus (AAV) vector-based gene therapy designed to silence the expression of the mutated SOD1 protein, which is toxic to motor neurons. The therapy is administered intrathecally as a one-time dose, using an AAVrh10 vector to deliver a microRNA (miRNA) that targets the disease-causing gene.

"We are pleased with the positive outcome of this initial IDMC meeting, which marks a meaningful step in the clinical development of AMT-162 for SOD1-ALS," said Walid Abi-Saab, MD, chief medical officer of uniQure. "We will continue to advance the study and look forward to proceeding with dose-escalation in the second cohort of patients."

The EPISOD1 trial (NCT06100276) is a multi-center, open-label study taking place in the United States. It is designed to evaluate three dose levels of AMT-162 before proceeding to a dose expansion phase involving approximately 6 to 8 patients. The trial aims to assess the safety and tolerability of AMT-162, as well as exploratory efficacy signals by measuring neurofilament light chain (a biomarker of neuronal damage) and SOD1 protein levels.

SOD1-ALS: An Unmet Need

SOD1-ALS is a rare, progressive, and fatal neurodegenerative disease characterized by the loss of motor neurons in the brain and spinal cord. As ALS progresses, patients experience muscle weakness and atrophy, leading to loss of mobility, speech, and eventually respiratory failure. Approximately 2% of the estimated 170,000 individuals with ALS globally have SOD1 mutations. The average life expectancy for those diagnosed with ALS is three to five years from the onset of symptoms.

uniQure's Broader Pipeline

In addition to AMT-162, uniQure is developing other AAV vector-based gene therapies for neurological indications, including AMT-130 for Huntington's disease. The FDA has agreed to consider data from ongoing Phase I/II studies of AMT-130, compared to external control natural history data, to support a biologics license application (BLA) under an accelerated approval pathway. The composite Unified Huntington’s Disease Rating Scale may serve as an intermediate clinical endpoint, with supportive evidence from cerebrospinal fluid neurofilament light chain decreases.