Amylyx advancing ALS treatment in trial after early safety data is positive
LUMINA to now test AMX0114 at higher doses; trial recruiting in US, Canada
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- AMX0114, an investigational therapy for ALS, showed safety and good tolerability at its lowest dose in a first-in-human clinical trial.
- Developer Amylyx is now advancing that trial, called LUMINA, to test higher doses of the treatment candidate.
- People with ALS are being recruited at 14 study sites in the U.S. and Canada.
The lowest tested dose of Amylyx Pharmaceuticals‘ treatment candidate AMX0114 was found to be safe and well tolerated among people with amyotrophic lateral sclerosis (ALS) in an ongoing Phase 1 clinical trial.
Biomarkers of nerve damage due to ALS remained relatively stable from the study’s start — a result the trial investigators believe may change with higher doses and longer treatment. The team noted that these “findings are not unexpected at this dose and timeframe and may reflect either insufficient exposure or duration.”
As such, Amylyx is now moving forward with testing higher doses, the company announced in a press release. The developer anticipates having four dosing groups in this first-in-human trial, dubbed LUMINA (NCT06665165).
While a second dosing group is fully enrolled, a third is now actively enrolling adults with ALS at 14 sites in the U.S. and Canada. To be eligible, a person’s symptoms must have started within the last two years.
The trial is testing the safety, tolerability, and pharmacological properties of the experimental therapy in adults with ALS.
The LUMINA data were presented at the European Network to Cure ALS (ENCALS) meeting, running this week in Spain, in a poster titled “Advancing AMX0114 for ALS: Updates from the LUMINA Phase 1 Study.”
In ALS, the nerve cells that control voluntary movement progressively die off, causing muscle weakness that affects movement, speech, swallowing, and breathing.
Treatment candidate AMX0114 aims to slow ALS progression
AMX0114 is a type of genetic medicine called an antisense oligonucleotide designed to reduce levels of calpain-2, an enzyme that is elevated in people with ALS and thought to promote nerve damage. In doing so, the treatment intends to slow neurodegeneration and disease progression.
The therapy has been granted fast track designation by U.S. regulators, a status intended to expedite the development of treatments for serious conditions with unmet medical needs.
In preclinical studies, AMX0114 lowered calpain-2 levels, improved nerve cell survival, and lowered biomarkers of nerve damage, prompting the launch of LUMINA in people with the progressive condition.
The trial aims to enroll 48 adults with ALS across four groups. In each, nine people will receive AMX0114, and three will be given a placebo. Treatment is given via injections into the spinal canal once every four weeks for a total of up to four doses, after which participants are monitored for about two more months.
In the first group, participants given AM0114 received the lowest dose being tested (12.5 mg); each subsequent group receives a higher dose. Across groups, participants may be receiving standard ALS medications, including riluzole (sold as Tiglutik and others) and/or Radicava ORS (edaravone).
Data from the low-dose group showed that the therapy was safe and well tolerated, with no serious medication-related side effects or neurological problems reported.
Most treatment-emergent side effects, such as headache and fatigue, were mild. Side effects related to the injection procedure were more common than medication-related side effects, and occurred with both AMX0114 and the placebo, according to the developer.
Biomarkers of nerve damage, including neurofilament light chain and phosphorylated neurofilament heavy chain, remained stable from the study’s start, as did levels of SBDP-145, a nerve damage biomarker that also directly reflects calpain activity. This lack of change was likely due to the low dose and short time frame, the researchers noted on the poster.
The second dosing group (25 mg) is fully enrolled and ongoing, while enrollment is underway for group 3 (50 mg). The dose for the fourth and final group has not been selected.
If safety and efficacy data support a favorable benefit-risk profile, Amylyx may implement an open-label extension of the trial, allowing eligible participants to continue receiving AMX0114.
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