Ionis Plans to Launch Clinical Trial This Year for ION582

Ionis Pharmaceuticals intends to launch a clinical trial later this year to test ION582, a potential Angelman syndrome therapy. 

The Phase 1/2a trial, designed to enroll up to 50 patients, is expected to start in the second half of 2021, Ionis wrote in a letter to the Angelman community, published on the website of the Foundation for Angelman Syndrome Therapeutics (FAST).

“We are completing the necessary preclinical studies with our lead compound and we are confident that we have selected [the] best compound to take forward as a potential treatment for the broadest Angelman syndrome population,” the letter said.

Although the letter itself did not state that the planned trial involves ION582, David Polk, Ionis’ executive director of corporate communications, confirmed that detail by phone with Angelman Syndrome News.

The company stated that the planned global study will enroll about 50 youths and adults, covering a broad age range.

The study’s primary goal is to assess the candidate therapy’s safety and tolerability. Participants will complete clinical assessments at their clinic visits, and parents and caregivers will be asked to complete questionnaires at home.

Ionis is now preparing for the trial’s launch by holding discussions with regulatory authorities, working on site selection, and developing Angelman-specific tools to best record and measure the potential changes that participants might experience in the trial.

“We are very grateful to all families who volunteer to take part in research and drug development efforts,” the company wrote. “We look forward to continuing our remarkable partnership with the community as we advance towards a treatment for Angelman syndrome. ”

Ionis also expressed its commitment to provide regular progress updates regarding the clinical trial process, activities related to the study’s launch, and any expected timelines.

ION582 is designed to “turn on” the paternal copy of the UBE3A gene.

While people receive two copies of most genes — one each from their mother and father — in certain areas of the brain, only the maternal UBE3A copy is active. The paternal copy of the gene is “silenced” by Ubiquitin Protein Ligase E3A-Antisense Transcript (UBE3A-ATS).

Angelman results when mutations in the maternal copy of the gene prevent functional UBE3A protein from being made. To counter that, ION582 works by blocking UBE3A-ATS, which “unsilences” the UBE3A gene.

Preclinical studies done in cells derived from Angelman patients and in a mouse model of the disorder have indicated that blocking UBE3A-ATS from interacting with the paternal UBE3A does effectively unsilence this gene. If this works in humans as well, it has the potential to restore UBE3A protein to healthy levels in the neurons of patients with Angelman.

Ionis said it wrote the letter to FAST to update the patient community on ION582.

“Last year was incredibly difficult on so many levels, and while 2021 will continue to have its challenges, we remain hopeful that our lives will begin to return to normal, and that there will be many great advancements towards a treatment for those living Angelman syndrome in the year ahead,” the company wrote.