Amylyx Pharmaceuticals ends AMX0035 trial for Progressive…

Amylyx Pharmaceuticals, Inc. recently made the announcement to discontinue the ORION program involving AMX0035 in adults affected by progressive supranuclear palsy (PSP). This decision comes after AMX0035 did not demonstrate any significant differences compared to a placebo on primary or secondary outcomes after 24 weeks. As a result, the Phase 2b trial and open-label extension will be halted, and there are no plans to move forward with the Phase 3 portion of the program.

Despite this disappointing outcome, the Company will continue to focus on their other research and development efforts, particularly the pivotal Phase 3 LUCIDITY trial of avexitide. This trial is expected to complete enrollment in 2025, with topline data anticipated in the first half of 2026. Additionally, Amylyx is also committed to the development of AMX0035 in Wolfram syndrome and AMX0114 in ALS, with early cohort data expected in 2025.

Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative disorder that impacts various aspects of movement, balance, eye movements, swallowing, and speech. Individuals diagnosed with PSP typically face a life expectancy of six to eight years after the initial diagnosis. With an incidence of approximately seven in 100,000 people globally, there are currently no approved therapies for the treatment of PSP.

AMX0035 is an oral combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO), with the aim of slowing or mitigating neurodegeneration by targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction. The safety profile of AMX0035 has been consistent with previous studies, and it has been generally well-tolerated. The Company believes that the data obtained from this trial will contribute to the existing literature on PSP and deepen scientific knowledge of this challenging condition.

In contrast, avexitide is a potential breakthrough therapy designed to address post-bariatric hypoglycemia (PBH). This condition affects an estimated 8% of individuals in the U.S. who have undergone bariatric surgery and can lead to debilitating hypoglycemic events and impaired quality of life. Avexitide binds to the GLP-1 receptor on pancreatic islet beta cells to decrease insulin secretion and stabilize blood glucose levels, thus reducing the incidence of hypoglycemic episodes.

The LUCIDITY trial is a Phase 3 clinical trial evaluating the efficacy and safety of avexitide in individuals with PBH following Roux-en-Y gastric bypass surgery. The trial aims to assess the impact of avexitide on reducing hypoglycemic events and improving overall quality of life for participants. With an up to six-week screening period and a 16-week double-blind treatment period, the trial is expected to provide valuable insights into the potential of avexitide as a treatment for PBH.

While the discontinuation of the ORION program for AMX0035 is a setback, the commitment of Amylyx Pharmaceuticals to advancing novel treatments for challenging conditions remains unwavering. The Company’s focus on cutting-edge research and development efforts underscores their dedication to improving the lives of individuals affected by rare and devastating diseases.