Amylyx’s AMX0114 Targeting Calpain-2 In Amyotrophic Lateral Sclerosis Receives FDA Fast Track Designation

Amylyx Pharmaceuticals has received Fast Track designation from the U.S. FDA for AMX0114, its experimental antisense oligonucleotide (ASO) therapy targeting calpain-2, aimed at treating amyotrophic lateral sclerosis (ALS). This designation is intended to accelerate the development and review of promising therapies for serious conditions with limited treatment options. 

“Obtaining FDA Fast Track designation for AMX0114 is an important step forward in our mission to develop potential treatments for people living with ALS, a relentlessly progressive and fatal disease with limited therapeutic options. This designation from the FDA recognizes both the seriousness of this devastating disorder and the encouraging preclinical evidence supporting AMX0114’s potential to target calpain-2, which has been found to be an important contributor to axonal degeneration, a critical driver in ALS progression. We are committed to advancing AMX0114 as quickly and efficiently as possible, and we continue to anticipate early cohort data from the Phase 1 LUMINA clinical trial later this year. We look forward to continued interaction with the FDA as we work to expeditiously advance the development of AMX0114, with the ultimate goal of addressing the urgent, unmet needs of the ALS community,” said Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx. 

AMX0114 is designed to inhibit calpain-2, a calcium-activated enzyme implicated in the breakdown of axons, nerve fibers responsible for transmitting signals. Overactivity of calpain-2 is believed to contribute significantly to ALS progression. In preclinical trials, AMX0114 improved neuronal survival and reduced levels of neurofilament light (NfL), a known marker of neurodegeneration, across various disease models.

A global, randomized, placebo-controlled trial known as LUMINA started in April 2025, led by Amylyx, looking at the safety, tolerability and biological effect of AMX0114 in patients with ALS. Nearly 48 people will be enrolled, and they will be randomly assigned a treatment of AMX0114 or a placebo by intrathecal injection every four weeks.  Early data from this study is expected later in 2025.