uniQure Begins Dosing in Phase I/II Trial of AMT-162 for SOD1-ALS Treatment

LEXINGTON, Mass. and AMSTERDAM, Oct. 15, 2024 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a prominent gene therapy enterprise addressing significant medical needs, has recently dosed the initial patient in the Phase I/II clinical trial of AMT-162. This trial targets amyotrophic lateral sclerosis (ALS) linked to mutations in superoxide dismutase 1 (SOD1), a rare and inherited progressive motor neuron disease.

Dubbed EPISOD1, the Phase I/II trial is an open-label, multi-center study based in the United States. It involves three dose-escalating cohorts that aim to evaluate the safety, tolerability, and preliminary efficacy signals of AMT-162 in SOD1-ALS patients.

Walid Abi-Saab, M.D., chief medical officer of uniQure, expressed his satisfaction with the dosing of the first patient. He highlighted that this trial represents the company's third gene therapy initiative to progress to clinical testing. The trial design seeks to promptly generate proof-of-concept data using established biomarkers, aligning with uniQure's objective of quickly delivering treatments to patients. AMT-162, an AAV-based gene therapy, aims to offer the convenience of a single dose, potentially presenting a unique efficacy profile for managing this devastating disease.

AMT-162 is an investigational therapy utilizing an AAVrh10 vector to deliver a microRNA intended to reduce the expression of the mutant SOD1 protein. Patients with SOD1-ALS produce a misfolded SOD1 protein that is toxic to motor neurons. This toxicity leads to muscle weakness, functional loss, and eventually death. AMT-162's one-time, intrathecal administration may provide a novel approach to slowing or stopping disease progression.

The U.S. Food and Drug Administration has granted AMT-162 both Orphan Drug status and Fast Track designation. The EPISOD1 trial involves up to twelve patients across three cohorts, with each patient receiving short-term immunosuppression before and after the drug's intrathecal infusion. The trial's primary objectives include assessing the safety and tolerability of AMT-162, as well as monitoring exploratory efficacy indicators through biomarkers such as neurofilament light chain and SOD1 protein levels. Currently, there are four active trial sites in the U.S., with plans to expand to seven more by early 2025.

SOD1-ALS is a rare, progressive, and fatal neurodegenerative condition. It results in the loss of motor neurons in the brain and spinal cord, leading to muscle weakness and atrophy. As the disease advances, patients lose mobility, speech, swallowing ability, and eventually the capacity to breathe, leading to respiratory failure. A 2021 study in Neuroepidemiology estimated that around 170,000 individuals globally have ALS, with SOD1 mutations accounting for about 2% of this population. The National Institute of Neurological Disorders and Stroke notes that ALS patients generally have a life expectancy of three to five years post symptom onset.

uniQure is committed to pioneering gene therapy solutions, aiming for single treatments with potentially curative outcomes. The company's gene therapy for hemophilia B marks a significant milestone in genomic medicine, ushering in new treatment possibilities for patients. uniQure continues to develop a pipeline of proprietary gene therapies targeting severe conditions, including Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and others.