AMT-162 gene therapy trial for SOD1-ALS set for next dose group
EPISOD1 study is intended to test three doses of therapy in ALS patients

uniQure is planning to start enrolling patients in a second dose group as part of a clinical trial testing AMT-162, its one-time gene therapy for amyotrophic lateral sclerosis (ALS) associated with mutations in the SOD1 gene.
The open-label Phase 1/2 study, called EPISOD1 (NCT06100276) is intended to test three doses of AMT-162 in people with SOD1-ALS. The trial started dosing last year with a first group given the lowest tested dose.
Data from that group have been reviewed by the trial’s independent data monitoring committee (IDMC), which is made up of external experts tasked with ensuring the safety of its participants. According to uniQure, the IDMC didn’t find any significant safety concerns and recommended the trial continue testing a higher dose in a second group.
“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,” Walid Abi-Saab, MD, chief medical officer of uniQure, said in a company press release.
Enrolling the second group of patients
The second cohort could start enrolling in the first quarter of 2025, according to uniQure. The EPISOD1 study is expected to enroll about 12 adults with a confirmed diagnosis of SOD1-ALS who meet certain criteria related to motor and lung function. Participants are allowed to continue certain standard ALS treatments, such as the riluzole-based medications Rilutek and Tiglutik, Radicava (edaravone), and Relyvrio (sodium phenylbutyrate and taurursodiol).
Patients taking Qalsody (tofersen), an approved treatment for SOD1-ALS, aren’t eligible to participate, however. Those who took Qalsody previously must have been off the drug for at least 20 weeks to be eligible for EPISOD1.
“We will continue to advance the study and look forward to proceeding with dose-escalation in the second cohort of patients,” Abi-Saab said.
The causes of ALS aren’t fully understood, but genetic mutations are believed to underlie the disease in some cases. Mutations in the SOD1 gene account for up to 1 in 5 cases of familial ALS and up to 1 in 50 cases of sporadic ALS. These mutations result in an abnormal version of the SOD1 protein being produced that forms toxic clumps in nerve cells, which damages them and leads to ALS symptoms.
When SOD1 is read to produce its protein, the genetic code is copied into a temporary molecule called messenger RNA, which travels to cells’ protein-making machinery and is then used as a template to make the protein.
AMT-162 uses a specially engineered virus to deliver a small piece of genetic material to cells that binds to and destroys the SOD1 messenger RNA. Doing this should reduce the amount of faulty SOD1 protein and slow the progression of SOD1-ALS.
uniQure acquired the rights to the gene therapy from Apic Bio in 2023. In a proof-of-concept study involving two men with SOD1-ALS, the gene therapy was given at a single dose of 420 trillion vector genomes together with an immunosuppressant to prevent immune responses against the viral vector.
The therapy was deemed safe. One man saw improvements in his ability to extend and flex his right leg and regained the ability to open and close his left hand before dying about 15.6 months after treatment started. The other patient had stable disease until the last follow-up at about 90 weeks, or about 1.7 years.