Last Participant Finishes PEGASUS Clinical Trial, Results Expected Next Year

The last participant has completed the planned 24 weeks in the Phase 2 PEGASUS clinical trial, which is assessing the safety and biological activity of Amylyx Pharmaceuticals‘ investigational therapy AMX0035 in people with Alzheimer’s disease.

Top-line results from the trial are expected in the first half of 2021.

“The PEGASUS trial design and broad inclusion criteria will allow us to assess whether AMX0035 can prevent neurodegeneration in people with Alzheimer’s via MR imaging and fluid biomarkers,” Steven E. Arnold, MD, trial principal investigator, and professor at Massachusetts General Hospital and Harvard Medical School, said in a press release.

“We are immensely thankful to the trial participants and their families for their time and commitment to this critical research effort,” he said.

AMX0035 is an oral formulation of sodium phenylbutyrate (PB) and tauroursodeoxycholic-acid (TUDCA). PB helps stop proteins from unfolding — protein unfolding is associated with the toxic accumulation of proteins in nerve cells. TUDCA helps to limit the loss of cellular energy, which is involved in the progression of neurological diseases like Alzheimer’s.

Amylyx reported encouraging results of the Phase 2 CENTAUR trial (NCT03127514), which assessed the compound’s safety and tolerability among 137 people with sporadic or familial amyotrophic lateral sclerosis, in 2019.

PEGASUS (NCT03533257) is testing the investigational medication’s safety and tolerability among people with late mild cognitive impairment or early dementia due to Alzheimer’s. The trial was sponsored by Amylyx, and also received funding from the Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, and Cure Alzheimer’s Fund.

Amylyx announced earlier this summer that the trial had completed enrollment, with 96 participants. The trial had originally planned to enroll 100 participants, but enrollment was capped early due to the COVID-19 pandemic. Site investigators and clinic teams worked with Amylyx to allow changes to the trial design (e.g., remote visits and expanded visit windows) to accommodate the pandemic when possible.

Participants in the trial were randomized to receive either AMX0035 or a placebo for 24 weeks (roughly six months). The study’s main goal is to investigate the treatment’s safety and tolerability, as assessed by reported adverse events. A battery of imaging-based markers, neurobiological changes, functional measures, and cognitive outcomes will also be assessed.

“The PEGASUS trial will assess the impact of investigational product AMX0035 on biomarkers in people with Alzheimer’s and hopefully lead to a future treatment,” said Rudolph Tanzi, PhD, professor at Harvard Medical School and founding chair of the Amylyx Scientific Advisory Board.

Kent Leslie, chief scientific officer at Amylyx, added: “Amylyx is committed to rigorous scientific research to improve people’s health, and we thank all patients, investigators, site teams, the Alzheimer’s Association, the Alzheimer’s Drug Discovery Foundation and Cure Alzheimer’s Fund for their contributions to the PEGASUS study milestone. We look forward to sharing the topline results of the trial in the first half of 2021.”