Masitinib is an investigational pharmaceutical compound. Its potential to influence specific cellular pathways makes it a subject of ongoing scientific investigation.
What Masitinib Is
Masitinib is a selective oral tyrosine kinase inhibitor (TKI). It was approved for treating mast cell tumors in dogs (commercial name Masivet) in Europe since 2009. In human medicine, masitinib remains an investigational drug, currently in clinical trials.
How Masitinib Works
Masitinib inhibits certain tyrosine kinases, enzymes involved in cell signaling. Its primary targets include c-Kit, Lyn, and Fyn kinases. By modulating these kinases, masitinib influences specific immune cells like mast cells, macrophages, and microglia. This regulates inflammatory responses and cellular processes in certain diseases.
Therapeutic Focus Areas
Masitinib is being investigated across oncology, neurological disorders, and inflammatory diseases.
Oncology
In oncology, it has been studied for mast cell tumors, gastrointestinal stromal tumors, prostate cancer, pancreatic cancer, melanoma, and multiple myeloma. Its mechanism of action, including targeting specific mutations and influencing the tumor microenvironment, explains its use in these cancers.
Neurological Disorders
In neurological disorders, masitinib is being studied for conditions like Amyotrophic Lateral Sclerosis (ALS), multiple sclerosis (MS), and Alzheimer’s disease. For ALS, it aims to reduce neuroinflammation and slow disease progression by inhibiting specific immune cells. In progressive forms of MS, masitinib targets microglia and mast cells, involved in the disease.
Inflammatory Conditions
Masitinib is also explored for inflammatory conditions, including systemic mastocytosis, rheumatoid arthritis, and severe asthma. Its ability to inhibit c-Kit, Lyn, and Fyn kinases is key here, as these kinases are involved in mast cell function and activation, contributing to inflammation.
Safety Profile
Clinical trials of masitinib show common adverse effects. These include gastrointestinal issues (nausea, diarrhea) and skin reactions (rash, pruritus). Other effects include edema (tissue swelling) and asthenia (weakness).
More serious, but less common, side effects include respiratory failure. A voluntary worldwide hold on clinical studies occurred in 2021 due to a potential risk of ischemic heart disease. Animal studies have indicated possible cardiac toxicity. The full safety profile for human indications is still under investigation.
Current Regulatory Landscape
Masitinib has conditional approval for veterinary use in some regions for mast cell tumors in dogs. For human use, it remains investigational, in clinical trials. It has received orphan drug designation in the U.S. and Europe for conditions like ALS, providing development incentives for rare diseases.
Despite ongoing research, masitinib has faced regulatory hurdles for human approval. The European Medicines Agency (EMA) recommended refusing marketing authorization for masitinib in ALS in 2018 and again in 2024, citing concerns about study reliability. Confirmatory Phase 3 trials are underway or planned for conditions like ALS and metastatic castrate-resistant prostate cancer to support future approvals.