The US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (NDA) for avapritinib (Ayvakit®) for the treatment of adult patients with indolent systemic mastocytosis (SM). The regulatory application is based on results from the global PIONEER trial—the largest randomized, placebo-controlled study conducted to date in individuals with SM.

The FDA previously granted Breakthrough Therapy designation to avapritinib for the treatment of patients with moderate to severe SM. The agent was designed to selectively and potently inhibit the KIT D816V mutation—the primary underlying cause of SM.

Avapritinib is marketed by Blueprint Medicines Corporation. According to Becker Hewes, MD, chief medical officer at Blueprint Medicines, “People with systemic mastocytosis experience debilitating symptoms and poor quality of life, and we have the potential to transform clinical outcomes for these patients by targeting the genetic driver of disease with Ayvakit.”

Treatment with avapritinib achieved the primary endpoint and all key secondary endpoints in PIONEER. Study findings showed highly meaningful reductions in patient-reported symptoms and all evaluated measures of mast cell burden, as well as a well-tolerated safety profile that was supportive of chronic treatment.

Learn more about SM

SM is a rare disease that is driven by the KIT D816V mutation in approximately 95% of cases. Patients with SM have an overproduction of abnormal mast cells. The uncontrolled proliferation and activation of mast cells results in chronic, severe, and often unpredictable symptoms in multiple organ systems.

Most affected individuals have nonadvanced (ie, indolent or smoldering) SM; the vast majority have indolent SM. Symptoms can include anaphylaxis, maculopapular rash, pruritus, diarrhea, brain fog, and bone pain. Currently, no treatments have been approved for patients with nonadvanced SM.

Dr. Hewes commented, “We look forward to collaborating with the FDA during its review process, with the goal of bringing the first approved medicine to patients with indolent SM and redefining the treatment landscape beyond symptom-directed therapies.”


Blueprint Medicines announces FDA acceptance of supplemental New Drug Application for Ayvakit® (avapritinib) for the treatment of indolent systemic mastocytosis. News release. Blueprint Medicines Corporation; January 23, 2023.