Amylyx Pharmaceuticals, Inc. has announced that the first participant has been dosed in the LUMINA trial, a Phase 1, multinational, randomized, double-blind, placebo-controlled, multiple ascending dose clinical trial of AMX0114. AMX0114 is an investigational antisense oligonucleotide (ASO) targeting calpain-2, designed for individuals living with amyotrophic lateral sclerosis (ALS). The company expects early cohort data from the LUMINA trial in 2025.

The LUMINA trial (NCT06665165) will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in ALS patients. It will also examine key ALS biomarkers, including changes in neurofilament light chain (NfL) levels. Approximately 48 participants from North America are expected to be enrolled, with a 3:1 randomization to receive either AMX0114 or placebo, administered intrathecally every four weeks for up to four doses.

AMX0114 targets calpain-2, a calcium-activated protease, which has been identified as a key factor in axonal degeneration. Research has shown that overactive calpain-2 may contribute to ALS progression by damaging axons, which transmit signals between neurons and muscles. Preclinical studies suggest that inhibiting calpain-2 could improve neuronal survival and reduce axonal degeneration.

Sabrina Paganoni, MD, PhD, principal investigator of the LUMINA trial, highlighted the urgent need for new ALS treatments, given the limited available options. She emphasized that AMX0114 could potentially address one of the main causes of axonal degeneration in ALS, bringing hope for a new treatment approach for people living with the disease.

Source: https://www.amylyx.com/news/amylyx-pharmaceuticals-announces-first-participant-dosed-in-phase-1-multiple-ascending-dose-lumina-trial-of-amx0114-in-people-living-with-amyotrophic-lateral-sclerosis