Masitinib for ALS
Last updated Dec. 9, 2024, by Marisa Wexler, MS
Fact-checked by Inês Martins, PhD
What is masitinib for ALS?
Masitinib is an oral medication being developed by AB Science as a potential add-on treatment for slowing disease progression in people with amyotrophic lateral sclerosis (ALS).
The therapy, formerly known as AB1010, successfully completed a Phase 2b/3 clinical trial involving ALS patients, and is now being tested in an ongoing Phase 3 trial.
AB Science previously filed for masitinib’s conditional approvals in Canada and in the European Union, but the responses on both continents were generally negative. The company is hoping that data from the confirmatory Phase 3 trial will support future applications to these and other regulatory agencies.
Masitinib has been granted orphan drug designation in the U.S. and Europe, a status that provides a range of incentives to boost the development and approval of therapies for rare diseases.
If an approval is ultimately granted, the medication will be marketed as Alsitek in both Canada and Europe. AB also is exploring masitinib as a potential treatment for a number of other conditions, including multiple sclerosis, Alzheimer’s disease, and several cancers.
Therapy snapshot
| Treatment name: | Masitinib |
| Administration: | Oral tablets |
| Clinical testing: | Completed a Phase 2b/3 trial, a Phase 3 study is ongoing |
How does masitinib work in ALS?
Masitinib belongs to a class of medications called tyrosine kinase inhibitors. As the name implies, it works by blocking the activity of tyrosine kinases, a group of proteins important for a number of cellular processes, such as cell maturation, growth, and death.
The medication specifically blocks tyrosine kinases that are essential for the function of certain immune cells, including macrophages, microglia, and mast cells. These are key cells of the innate immune system — a part of the immune system that serves as a first line of defense against infections — that are thought to drive inflammation and neurodegeneration in ALS.
It’s not known exactly what causes ALS, but numerous studies have suggested that uncontrolled inflammation may play a role. By blocking the activation of these immune cells, masitinib may help to reduce inflammation and slow ALS disease progression.
How will masitinib be administered in ALS?
Masitinib is available in the form of film-coated tablets that, in ALS clinical trials, were administered orally twice daily. The medicine has been tested at doses ranging from 3-6 mg/kg per day, but an ongoing Phase 3 trial is investigating daily doses of 4.5 and 6 mg/kg.
In all ALS trials to date, masitinib has been given as an add-on to the approved ALS treatment Rilutek (riluzole).
Masitinib in ALS clinical trials
In preclinical studies, masitinib significantly reduced inflammation, eased neurodegeneration, and extended survival in a mouse model of ALS. This led AB Science to begin testing the therapy in clinical trials involving ALS patients.
Phase 2/3 AB10015 trial
An initial Phase 2/3 clinical trial, called AB10015 (NCT02588677), enrolled 394 people with ALS whose symptoms had begun in the previous three years. Most had normal disease progression, as measured by changes in the ALS Functional Rating Scale-Revised, known as ALSFRS-R. These so-called normal progressors had an ALSFRS-R decline rate of less than 1.1 points per month from disease onset to the study’s start.
The participants were randomly assigned to receive either a placebo or masitinib for 48 weeks, or nearly one year. The daily dose of masitinib was 3 or 4.5 mg/kg, and it was given as an add-on to Rilutek.
The study’s main goal was to determine if treatment could slow disease progression, as assessed by ALSFRS-R, in normally progressing patients who received the higher dose.
The results showed that, in these patients, masitinib significantly reduced the rate of progression, by about 27%, compared with the placebo. That higher dose also significantly slowed declines in lung function and quality of life in patients progressing normally.
The greatest benefits, however, were seen in normal progressors with mild or moderate ALS — defined as a score of two or higher on every item of the ALSFRS-R upon entering the trial. For those patients, masitinib slowed the rate of disease progression by 42%. The median overall survival time for these individuals also was significantly longer with masitinib than with the placebo (69 months vs. 44 months). That difference, of more than two years, represented a 44% reduction in the risk of death.
No significant benefit in disease progression or survival rates was detected when normal and fast-progressing patients were examined together, irrespective of masitinib doses.
Ongoing Phase 3 trial
AB Science now is sponsoring a Phase 3 clinical trial (NCT03127267), called AB19001, that is expected to include an estimated 495 adults with ALS who are less than two years out from a disease diagnosis.
The study is being conducted at sites across the U.S., Europe, and Israel. It involves people with mild to moderate ALS who are on stable treatment with Rilutek.
Participants will be randomly assigned to take a daily dose of masitinib (4.5 or 6 mg/kg) or a placebo, for 48 weeks. For the first four weeks, or about one month, those assigned to masitinib will receive the treatment twice daily, at a 3 mg/kg daily dose, after which they will escalate to the 4.5 mg/kg dose. Individuals in the higher dose group will then further increase their dose to 6 mg/kg a day after four weeks on the intermediate dosage.
The trial’s main goal is to assess the effect of treatment on disease progression, as measured by changes in ALSFRS-R scores. As in the previous trial, participants will be divided into normal or fast progressors based on the cutoff ALSFRS-R score of 1.1 points.
Other outcomes that also will be assessed include the therapy’s impact on quality of life, and its effect on lung function, muscle strength, and survival.
Common side effects of masitinib
In ALS clinical trials, the most commonly reported side effects of masitinib include:
- rash
- tissue swelling, or edema
- respiratory failure
- nausea
- diarrhea
- anxiety.
ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about masitinib
Masitinib is an experimental oral therapy being investigated in clinical trials as a potential treatment for amyotrophic lateral sclerosis (ALS). It works by blocking specific proteins called tyrosine kinases, which is expected to reduce the inflammation thought to be involved in ALS progression. In ALS clinical trials, the therapy helped to slow functional decline and significantly extended survival in a subgroup of patients.
At present, it is too early to determine if or when masitinib might be up for approval by the U.S. Food and Drug Administration. The therapy has been submitted for conditional approval in Europe and in Canada, but Health Canada rejected the application and a European committee recommended against approval twice.
The most common side effects reported in amyotrophic lateral sclerosis clinical trials of masitinib included rash, tissue swelling, respiratory failure, nausea, diarrhea, and anxiety. Yet, because the drug is still in clinical testing, its full safety profile may not be fully known. Patients taking masitinib should discuss the potential side effects of the medication with their healthcare provider.
The interaction between masitinib and alcohol has not been studied in-depth. It’s recommended patients talk to their healthcare team about whether and how much is safe for them to drink while taking any medication.
In a Phase 2/3 trial, a significant difference in amyotrophic lateral sclerosis progression rates was evident between masitinib and a placebo in a subgroup of patients after about a year of treatment. However, each person may respond differently to the medication, so patients should ask their healthcare team how the treatment may affect them.
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