Calpain-2 Targeting Antisense Oligonucleotide Fast Tracked for ALS

The Food and Drug Administration (FDA) has granted Fast Track designation to AMX0114 for the treatment of amyotrophic lateral sclerosis (ALS).

AMX0114 is an investigational antisense oligonucleotide targeting calpain-2 (CAPN2), a calcium-activated protease believed to play a role in ALS disease progression. In preclinical studies, reductions in CAPN2 mRNA and calpain-2 protein levels were observed with AMX0114, demonstrating an improvement in neuronal survival and a decrease in extracellular neurofilament light levels across multiple disease models.

A phase 1 trial, LUMINA (ClincialTrials.gov Identifier: NCT06665165), is currently underway and is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in approximately 48 patients with ALS. Study participants will be randomly assigned 3:1 to receive AMX0114 or placebo once every 4 weeks by intrathecal bolus injection for a total of up to 4 doses. 

The primary outcome of the study is an evaluation of safety and tolerability. The trial will also assess the effects of AMX0114 on biomarkers of ALS, including markers of neuronal death and neuroinflammation. Amylyx recently announced that the first participant has been dosed in the LUMINA trial; early cohort data is expected in 2025.   

“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,” said Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx. “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.”

This article originally appeared on MPR