uniQure Doses First Patient in Phase I/II Trial of AMT-162 for SOD1-ALS

LEXINGTON, MA, USA and AMSTERDAM, The Netherlands, October 15, 2024 – uniQure N.V. (NASDAQ: QURE), a prominent gene therapy company, has announced the first dosing of a patient in the Phase I/II clinical trial of AMT-162. This investigational gene therapy targets amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) mutations, a rare and progressive motor neuron disease. The EPISOD1 trial, a Phase I/II study, is being conducted across multiple centers in the United States, employing an open-label design with three dose-escalating cohorts. The primary aim is to assess the safety, tolerability, and preliminary effectiveness of AMT-162 in patients with SOD1-ALS.

Dr. Walid Abi-Saab, chief medical officer of uniQure, expressed enthusiasm about this milestone, stating, "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. 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 to bring treatments to patients as quickly as possible. 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."

AMT-162 is an investigational gene therapy based on the AAVrh10 vector, which expresses a microRNA designed to suppress the expression of the mutated SOD1 protein. In SOD1-ALS patients, the SOD1 protein is misfolded, leading to motor neuron toxicity, which causes muscle weakness, loss of function, and ultimately death. AMT-162 aims to provide a novel, one-time intrathecal treatment that could slow or halt SOD1-ALS progression. The U.S. Food and Drug Administration has granted AMT-162 both Orphan Drug status and Fast Track designation.

The EPISOD1 trial in the United States will involve three cohorts, with up to four patients each. Participants will receive a short course of immunosuppression before and after the intrathecal infusion of AMT-162. The trial will evaluate the safety and tolerability of AMT-162 and will measure exploratory signs of efficacy, focusing on biomarkers such as neurofilament light chain and SOD1 protein. Currently, four sites are active in the U.S., with plans to activate seven more by early 2025.

Amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations is a rare, progressive, and fatal neurodegenerative disorder. It leads to the degeneration of motor neurons in the brain and spinal cord. As the disease advances, patients experience muscle weakness and atrophy, losing the ability to move, speak, swallow, and breathe, eventually leading to respiratory failure. A 2021 study in Neuroepidemiology estimated around 170,000 individuals globally have ALS, with SOD1 mutations accounting for 2% of this population. The National Institute of Neurological Disorders and Stroke notes that the average life expectancy for ALS patients is three to five years from symptom onset.

uniQure is pioneering gene therapy with single treatments that potentially offer curative results. The company has achieved major milestones, including the approval of its gene therapy for hemophilia B, based on over a decade of research and clinical development. This breakthrough paves the way for new treatment paradigms in genomic medicine. uniQure is also progressing a pipeline of gene therapies targeting Huntington’s disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe conditions.