Amylyx Begins Phase 1 LUMINA Trial of AMX0114 for ALS with First Dosing

Amylyx Pharmaceuticals, based in Cambridge, Massachusetts, has initiated a significant clinical trial titled LUMINA, focusing on a novel treatment for amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease. This trial involves AMX0114, an investigational antisense oligonucleotide (ASO) specifically designed to inhibit calpain-2, a protease implicated in the pathway of axonal degeneration, which is a key factor in ALS progression.

The LUMINA trial is a Phase 1 study that is multinational, randomized, double-blind, and placebo-controlled. It aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114. The study is set to enroll around 48 participants from North America who are living with ALS. Participants in the trial will be randomly assigned in a 3:1 ratio to receive either AMX0114 or a placebo, administered intrathecally every four weeks, up to four doses in total.

The research is driven by the hypothesis that calpain-2 plays a significant role in the degradation of axons, which are critical for transmitting signals in neurons. Overactivity of calpain-2 has been identified as a potential contributor to the progression of ALS, as well as other neurodegenerative disorders. By targeting this protease, AMX0114 aims to curb axonal degeneration and promote neuronal survival. Preclinical studies have indicated that inhibiting calpain-2 can lead to improved outcomes, such as decreased levels of neurofilament light chain (NfL), a biomarker for neurodegeneration, and enhanced neuronal survival across multiple disease models.

Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx, expressed enthusiasm about advancing AMX0114 into clinical trials for ALS patients. The company aims to develop a therapeutic option that can potentially alter the course of this progressive and currently incurable disease. Sabrina Paganoni, MD, PhD, the principal investigator for the LUMINA trial, emphasized the critical need for new therapeutic approaches that address the underlying mechanisms of ALS, given the limited existing treatment options.

ALS is characterized by the progressive degeneration and death of motor neurons in the brain and spinal cord, leading to muscle weakness, loss of voluntary movement, speech difficulties, respiratory failure, and ultimately, death. Most ALS cases are sporadic, with no evident familial linkage, and the disease remains fatal as there are no definitive cures.

In summary, Amylyx Pharmaceuticals is spearheading a pivotal study to explore the potential of AMX0114 as a treatment for ALS. If successful, this could mark a significant breakthrough in the therapeutic landscape for ALS and other neurodegenerative diseases. The company anticipates obtaining early cohort data from the LUMINA trial within the year, highlighting its commitment to addressing the urgent needs of the ALS community with innovative scientific solutions.