AB Science adds new biomarker to Phase 3 masitinib ALS clinical trial
Company says marker may help validate mechanism and identify responders
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- AB Science identified a new blood biomarker to assess masitinib activity in ALS.
- The marker is linked to pro-inflammatory immune cells involved in ALS-related inflammation.
- It will be incorporated into the Phase 3 trial to help evaluate response to treatment.
AB Science has identified a new blood biomarker, produced by certain immune cells, that may help assess the activity of its experimental therapy masitinib in people with amyotrophic lateral sclerosis (ALS).
The biomarker, which the company did not disclose for patent protection reasons, is capable of identifying patients with pro-inflammatory microglia — the brain’s resident immune cells — which are believed to contribute to inflammation and nerve cell damage in ALS.
In a press release, AB Science said the biomarker will be introduced into its ongoing Phase 3 development program for masitinib, including the Phase 3 AB23005 trial (NCT07174492), which has been cleared to begin in the U.S. and Europe. The study will test masitinib in combination with riluzole (sold as Tiglutik and generics) in about 412 adults with ALS.
Biomarker addition aligns with regulatory guidance
The decision to add the biomarker is in line with U.S. Food and Drug Administration (FDA) guidance on ALS drug development, which encourages companies to include exploratory biomarkers throughout all phases of clinical testing.
According to the FDA, advances in scientific understanding may eventually allow certain biomarkers to serve as surrogate endpoints — measures reasonably likely to predict clinical benefit and potentially support accelerated approval.
By integrating the newly identified biomarker into its Phase 3 program, AB Science says it aims to validate masitinib’s mechanism of action and potentially determine which patients respond best to treatment, which could inform future regulatory discussions.
ALS is caused by the dysfunction and death of motor neurons — the nerve cells that control voluntary movement — leading to progressive loss of muscle control and the ability to perform everyday tasks.
Masitinib is an oral therapy being developed as an add-on treatment intended to slow ALS progression. It works by inhibiting tyrosine kinases, enzymes involved in the activity of immune cells such as microglia and mast cells, which are believed to contribute to inflammation and nerve cell damage in ALS.
According to the company, the newly identified biomarker is produced by pro-inflammatory microglia and mast cells and promotes a pro-inflammatory state in microglia and astrocytes — support cells in the nervous system. The company says this contributes to a vicious cycle of increasing brain inflammation and disease progression.
Preclinical data suggest link to inflammation and survival
In lab experiments, levels of the biomarker decreased when activated microglia and mast cells were treated with masitinib, suggesting the therapy directly targets these inflammatory cells. The biomarker was also reported by the company to predict survival in ALS, which AB Science said may help explain why masitinib was associated with extended survival in some patients in earlier studies.
“Interestingly, this biomarker could be used in ALS but also in other neurodegenerative diseases of interest, namely progressive forms of multiple sclerosis (MS) and Alzheimer’s disease,” said Olivier Hermine, MD, president of AB Science’s scientific committee.
Masitinib is also in Phase 3 testing in these two indications, and the biomarker will similarly be included in those studies.
Masitinib’s development in ALS builds on findings from an earlier Phase 2/3 clinical trial (NCT02588677), which tested the therapy as an add-on to riluzole compared with placebo.
In that study, a 4.5 mg/kg dose of masitinib was associated with a 27% slowing of disease progression over about one year in patients classified as normal progressors. The greatest benefit was reported in patients with mild to moderate disease, in whom progression was slowed by 42% and survival was extended by more than two years.
AB Science later launched a confirmatory Phase 3 trial, AB19001 (NCT03127267), intended to support a potential regulatory submission. However, that study faced recruitment challenges and was ultimately discontinued before completion.
New Phase 3 trial designed after regulatory feedback
Following discussions with U.S. and European regulators, the company designed AB23005 to address limitations from the earlier study. In line with the group that benefited most from masitinib in the earlier trial, eligible participants must have normally progressing disease and not have completely lost physical function.
Participants will be randomly assigned to receive masitinib or a placebo for 48 weeks, in addition to standard riluzole treatment. Masitinib will start at 3 mg/kg per day, given orally in two divided doses, which will be increased over one month to the target dose of 4.5 mg/kg per day, pending safety evaluation.
The trial’s main goal is to assess whether masitinib can slow disability progression, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary endpoints include time to disease progression — defined as a decline of more than nine ALSFRS-R points — or death, and changes in quality of life.
