Masitinib (formerly known as AB1010) is an oral immunomodulatory drug (one that changes the activity of the immune system), which is being developed as a possible treatment for progressive forms of multiple sclerosis (MS) and other diseases, such as amyotrophic lateral sclerosis (ALS). Its developer, AB Sciences, is currently testing its safety and effectiveness in clinical trials for a number of conditions. The drug has been designated an Orphan Drug by the U.S. Food and Drug Administration (FDA) as a potential ALS treatment.
How masitinib works
Masitinib belongs to a class of chemical compounds known as tyrosine kinase inhibitors (TKI). Tyrosine kinases are enzymes responsible for the activation of proteins vital to several cell-signaling processes related to the growth, division, and proliferation. Masitinib is a selective TKI, which blocks the activity of specific tyrosine kinases in particular immune cells such as macrophages and mast cells.
Mast cells are believed to play an important role in MS, in which the immune system mistakenly attacks the myelin sheath (a protective layer that surrounds the nerve fibers), resulting in disrupted nerve signaling. The damage is caused by immune cells, such as T-cells targeted to myelin, migrating through the blood brain barrier (BBB) and causing inflammation. Mast cells have multiple roles in the immune response, including breaking down the BBB to allow the T-cells to access the nerves. The mast cells may also be involved in recruiting and stimulating T-cells to attack myelin.
By inhibiting cell signaling in the mast cells, masitinib acts to reduce activated T-cells from accessing the nervous system, reducing the inflammatory response and the damage that leads to the symptoms of MS.
Masitinib in clinical trials
A proof-of-concept, 18-month Phase 2 study (NCT01450488) in 35 patients with primary or secondary forms of progressive MS was completed in 2011. The results did not show a statistically significant difference between patients treated with masitinib or placebo, but there were promising indications that justified its continued testing. The results of the trial were published in the scientific journal, BMC Neurology.
A Phase 2/3 double-blind, randomized, placebo-controlled study (NCT01433497) is currently assessing the safety and effectiveness of masitinib over a 96-week period in people with primary progressive MS (PPMS) or relapse-free secondary progressive MS (SPMS).
The main objective is to assess the effectiveness of masitinib via changes in Multiple Sclerosis Functional Composite (MSFC), a three-part assessment system that measures changes in leg function and walking ability, arm and hand function, and cognitive function, and assigns a standardized score.
The secondary objectives include evaluating changes to quality of life measured by the Multiple Sclerosis Quality of Life-54 (MSQOL-54) assessment and the level of disability. The Expanded Disability Status Scale (EDSS) method is used to quantify disability in multiple sclerosis and monitor changes in the level of disability over time.