ALS medication AMX0114 shows safety, moves to 2nd trial group
Treatment well tolerated in 1st 12 LUMINA trial participants
- AMX0114, an experimental ALS medication, showed safety and was well tolerated in initial trial participants.
- The drug aims to reduce calpain-2, an enzyme linked to nerve fiber degeneration in ALS.
- The clinical trial is now progressing to test a higher dose of AMX0114 in a second patient group.
AMX0114, being developed as an amyotrophic lateral sclerosis (ALS) medication, has been well tolerated in early clinical testing, and a second group of patients will now test a higher dose of the experimental treatment.
The first group of 12 participants enrolled in the Phase 1 LUMINA clinical trial (NCT06665165) received four monthly injections of either a low dose of AMX0114 (12.5 mg) or a placebo, with the main goal of assessing safety. No serious side effects or neurological issues were reported.
The interim trial data were presented at the 36th International Symposium on ALS/MND (MNDA), held Dec. 5-7 in San Diego, in a poster titled, “A Phase 1, Multicenter, Randomized, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of AMX0114 in Amyotrophic Lateral Sclerosis (LUMINA).”
“We appreciate the partnership with LUMINA sites and participants to achieve complete enrollment of the first cohort,” Camille L. Bedrosian, MD, chief medical officer of developer Amylyx Pharmaceuticals, said in a company press release. “In addition, we are pleased that to date no drug-related SAEs or dose-limiting toxicities were observed, which represent important early steps in this study.”
With these data in hand, Amylyx plans to enroll the second, higher-dose group beginning later this month at Canadian sites and in January at U.S. sites.
‘No time to wait’
“LUMINA is a first-in-human study, and we are encouraged by these data as we continue to advance AMX0114 as a potential treatment for this rapidly progressive disease with high unmet need,” said Sabrina Paganoni, MD, PhD, principal investigator of the LUMINA trial and physician scientist at the Sean M. Healey & AMG Center for ALS at Mass General Brigham. “The safety and tolerability analysis allows LUMINA to proceed with its next cohort of participants, which is critical given that this community has no time to wait.”
AMX0114 is an antisense oligonucleotide designed to prevent or slow the degeneration of nerve fibers by reducing levels of calpain-2, an enzyme that tends to be elevated in people with ALS and promotes nerve fiber damage.
In preclinical studies, AMX0114 reduced calpain-2 levels and enhanced nerve cell survival across multiple disease models, including a mouse model of ALS. It also reduced neurofilament light chain (NfL), a biomarker of nerve cell injury.
“AMX0114 is designed to inhibit calpain-2, a calcium-activated protease that is one of the fundamental drivers of [nerve fiber] degeneration and consequent disease progression in ALS,” Bedrosian said. “Preclinical studies have demonstrated that treatment with AMX0114 resulted in potent, dose-dependent, and durable reduction in calpain-2 protein levels, translating to improved neuronal survival and reductions in extracellular NfL levels.”
The ongoing trial is designed to enroll 48 participants across four dosing groups. In each group, nine patients will be randomized to receive an increasing dose of AMX0114, while three will receive a placebo.
Treatment will be given every four weeks, via an injection into the spinal canal, for a total of four doses. After completing the randomized part, participants may be eligible to join an open-label extension portion, which will last approximately eight weeks. The extension is pending positive safety and efficacy data from the earlier portion of the trial.
The main goal is to assess safety, but researchers will also examine changes in ALS biomarkers, as well as preliminary evidence suggesting AMX0114 may be able to slow disease progression, as assessed by changes in functional ability and lung function.
“We look forward to presenting cohort 1 biomarker data at a medical meeting in the first half of next year,” Paganoni said.
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