Amylyx Pharmaceuticals, Inc. announced an upcoming presentation at Neuro2023 on the design of ORION, a planned global, Phase 3 clinical trial of AMX0035 (sodium phenylbutyrate and taurursodiol [PB&TURSO]) in progressive supranuclear palsy (PSP). Neuro2023: The PSP and CBD International Research Symposium will take place on October 19, 2023 to October 20, 2023, at the Pan Pacific Hotel in London, UK. ORION Trial Design: ORION is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 compared to placebo.

Approximately 600 participants will be enrolled across North America, Europe, and Japan, with study initiation anticipated by the end of 2023 starting in the United States. The primary efficacy endpoint evaluates change in disease progression from baseline to Week 52 as measured by total score on the 28-item Progressive Supranuclear Palsy Rating Scale (PSPRS), an established and validated endpoint in PSP clinical trials. Secondary efficacy endpoints are disease progression as measured by a modified 10-item PSPRS score and motor aspects of activities of daily life as measured by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 2 (MDS-UPDRS Part II).

Exploratory outcomes include changes in activities of daily living, cognitive function, quality of life, overall survival, brain regional volumes, fluid biomarkers of neuronal injury/inflammation, and caregiver burden. Safety and tolerability will be evaluated by assessing the frequency of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). The ORION Phase 3 trial was designed and planned in collaboration with key global academic leaders, people living with PSP, and industry advocacy groups.

Additional key elements of the study design: The study will enroll ambulant adults, 40-80 years of age, with probable or possible PSP (also known as Richardson?s syndrome) according to International Parkinson and Movement Disorder Society 2017 criteria and less than 5 years since developing PSP symptoms. Key eligibility criteria include: A score of <40 on the 28-item PSPRS; A score of =24 on the Mini Mental State Examination; Study partner required; No feeding tube use; and On stable dose of antiparkinsonian drugs for 60 days before enrollment. After a screening period, participants will be randomized in a 3 to 2 manner to receive AMX0035 or matching placebo for 52 weeks (randomized phase). For all participants who complete the randomized phase, a 52-week open label extension phase will be available for continued access to AMX0035 to further characterize the long-term efficacy and safety of AMX0035 in this population.

Additional details regarding trial enrollment and eligibility criteria will be shared upon initiation of the trial, which is anticipated to start by the end of 2023.