Clinical hold lifted from Phase 1 trial of ALS therapy AMX0114
FDA placed hold after Amylyx sought permission for higher starting dose
The U.S. Food and Drug Administration (FDA) has lifted the clinical hold on a Phase 1 clinical trial that’s testing AMX0114, Amylyx Pharmaceuticals’ investigational treatment for amyotrophic lateral sclerosis (ALS).
The hold came in November after Amylyx asked to initiate the first-in-human studies for AMX0114 at a starting dose of 12.5 mg. The FDA restricted dosing to an amount lower than that and asked additional questions, resulting in the regulatory pause.
With the hold lifted, Amylyx will now be able to start screening and enrolling ALS patients across clinical sites in the U.S. for its upcoming Phase 1 LUMINA trial (NCT06665165), which is expected to start in Canada in the coming months, the company said in a press release.
The trial will enroll about 48 participants who will be randomly assigned to receive AMX0114 or a placebo via intrathecal injection, that is, into the spinal cord. Participants will receive up to four injections of their assigned treatment, given four weeks apart. For every person assigned a placebo, three will receive the therapy, which will be tested at multiple doses.
What is AMX0114; what is LUMINA study measuring?
LUMINA’s main goal is to determine the safety and tolerability of AMX0114. Other measures include its pharmacological properties, namely how it moves into, through, and out of the body, changes in ALS biomarkers, and disease progression.
“We are dedicated to investigating therapies to potentially treat people living with ALS, and we are excited to work with study investigators and clinical trial sites across North America to enroll participants in LUMINA,” said Camille L. Bedrosian, MD, Amylyx’s chief medical officer.
AMX0114 is an antisense oligonucleotide (ASO) that’s designed to prevent or slow the degeneration of axons, the long, wire-like extensions of nerve cells that transmit electrical signals, which contributes to the progression of ALS. It works by reducing levels of calpain-2, a protein that’s active in axonal degeneration and is elevated in ALS patients. In animal models, inhibiting calpain-2 has shown therapeutic benefit.
The therapy is designed to bind and promote the degradation of calpain-2’s messenger RNA (mRNA), a template molecule that’s produced when the gene is read and is used by the cell’s machinery to make the protein. By targeting these mRNA molecules for degradation, calpain-2 levels are reduced, which should improve nerve health.
Previous preclinical data have supported this approach, with AMX0114 preventing axonal degeneration and reducing markers of cell death in nerve cells exposed to harmful chemicals.
“Based on several preclinical efficacy studies and what is known about the central role of calpain-2 in the process of axonal degeneration, we believe AMX0114 has the potential to be a treatment for ALS and other diseases,” Bedrosian said.
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