Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. In the study, it was administered orally at 6 mg/kg per day in two daily doses over 24 weeks. The primary endpoint of cumulative response was defined as a ≥75% improvement from baseline within weeks 8–24 in at least one severe baseline symptom from the following: pruritus score of ≥9, ≥8 flushes per week, Hamilton Rating Scale for Depression of ≥19, or Fatigue Impact Scale of ≥75.
Systemic mastocytosis is a group of rare diseases characterised by accumulation of mast cells in the bone marrow or other internal organs, and is classified into four major categories. Indolent systemic mastocytosis is usually of good prognosis, whereas the three other categories—collectively termed advanced systemic mastocytosis—share a poorer prognosis. Symptoms are related to increased release of mast cell mediators, and can usually be controlled by antimediator therapies except in a subset of severely symptomatic patients.
A commentary notes that these data offer high hopes for masitinib, which could become an attractive alternative to the therapeutic arsenal available for patients with severely symptomatic indolent or smouldering systemic mastocytosis.
Masitinib currently has orphan drug status in the EU and US for the treatment of indolent systemic or cutaneous mastocytosis.