NEW YORK – Amylyx Pharmaceuticals announced this week that it has dosed the first amyotrophic lateral sclerosis (AML) patient with its investigational antisense oligonucleotide therapy (ASO), AMX0114, in a Phase I trial.
Amylyx designed the ASO to target mRNA encoding the calcium-activated protease calpain-2 protein. Increased calpain-2 activity is thought to degrade and possibly destroy the axons that carry signals from neurons to muscles or to other neurons in neurological diseases, including ALS. By reducing calpain-2 levels, the company hopes to slow the disease process.
Cambridge, Massachusetts-based Amylyx is enrolling about 48 patients with ALS from across North America into the Phase I LUMINA study, in which patients will be randomized 3:1 to receive AMX0114 or placebo once every four weeks by intrathecal bolus injection for a total of up to four doses.
In the trial, investigators will track the safety and tolerability of AMX0114 as well as certain ALS biomarkers. In particular, they will assess changes from baseline in calpain-2 levels in cerebrospinal fluid (CSF) and changes in neurofilament light levels in CSF and plasma. The company expects early cohort data from the trial this year.
"AMX0114 represents a potential therapeutic approach to inhibiting one of the fundamental drivers of axonal degeneration," said Sabrina Paganoni, principal investigator of the LUMINA trial and an investigator at Massachusetts General Hospital's ALS center, in a statement. "Dosing the first participant in LUMINA is a step toward a potential treatment option for people living with ALS and their loved ones."
In January, the US Food and Drug Administration lifted a clinical hold it had placed on the Phase I trial. The agency had requested more data on Amylyx's proposed starting dose for AMX0114.
Amylyx previously developed Relyvrio (sodium phenylbutyrate and taurursodiol), also known as AMX0035, as a treatment for ALS but removed it from the market in 2024, following disappointing results from the Phase III PHOENIX trial. The firm continues to study AMX0035 as a treatment for two rare diseases, Wolfram syndrome in the Phase II Helios trial and progressive supranuclear palsy in the Phase IIb/III ORION trial.