FDA Accepts Supplemental NDA for Avapritinib in Indolent Systemic Mastocytosis

Data from the phase 2 PIONEER trial supports the supplemental new drug application for avapritinib in adult patients with indolent systemic mastocytosis, an uncontrolled proliferation and activation of mast cells.

The FDA has accepted and granted priority review to a supplemental new drug application for avapritinib (Ayvakit) with an indication for adult patients with indolent systemic mastocytosis, according to a press release from Blueprint Medicines.1

The regulatory application was supported by data from the phase 2 PIONEER trial (NCT03731260) in which investigators evaluated the efficacy and safety of avapritinib plus best supportive care compared with placebo and best supportive care in patients with indolent systemic mastocytosis.

The FDA has issued a Prescription Drug User Fee Act date of May 22, 2023 for avapritinib.

“[Avapritinib] achieved the primary and all key secondary endpoints in the PIONEER trial, with highly meaningful reductions in patient-reported symptoms and all measures of mast cell burden studied, and a well-tolerated safety profile supporting chronic treatment,” Becker Hewes, MD, chief medical officer at Blueprint Medicines, said in the press release.

Investigators of the randomized, double-blind, placebo-controlled phase 2 PIONEER trial randomly assigned patients to either receive avapritinib or matched placebo administered orally in continuous 28-day cycles with best supportive care.

The primary end points of the trial included determining the recommended phase 2 dose and the mean change in indolent systemic mastocytosis Symptom Assessment Form scores on a scale of 0 to 100 points, with a higher score reflecting worse symptom outcomes. Secondary end points included the proportion of patients with at least 50% reduction in serum tryptase, changes in KIT D816V allele burden in blood, and changes in bone marrow mast cells.

Patients 18 years and older with systemic mastocytosis confirmed by Central Pathology Review of bone marrow biopsy and central review of B- and C-findings by World Health Organization diagnostic criteria were eligible for enrollment on the trial. Additional inclusion criteria included having moderate-to-severe symptoms of indolent systemic mastocytosis, being unable to achieve adequate symptom control for 1 or more baseline symptoms, and having an ECOG performance status of 0 to 2.

Patients diagnosed with systemic mastocytosis subclassifications including cutaneous mastocytosis, smoldering systemic mastocytosis, mast cell leukemia, or mast cell sarcoma were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had received prior treatment with avapritinib, received any cytoreductive therapy within 14 days of beginning study eligibility assessments, or received any hematopoietic growth factor within 14 days of beginning study eligibility assessments.

Previously, the FDA granted approval to avapritinib for adult patients with advanced systemic mastocytosis in June, 2021.2 The approval was supported by data from the phase 1 EXPLORER trial (NCT02561988) and the phase 2 PATHFINDER trial (NCT03580655), both of which included patients with advanced systemic mastocytosis.

The combined overall response rate among all evaluable patients who received 200 mg of avapritinib in the EXPLORER and PATHFINDER trials was 57% (95% CI, 42%-70%), with 28% of patients achieving complete remissions and 28% achieving partial remissions.


  1. Blueprint Medicines announces FDA acceptance of supplemental new drug application for AYVAKIT® (avapritinib) for the treatment of indolent systemic mastocytosis. News release. Blueprint Medicines. January 23, 2023. Accessed January 23, 2023. bit.ly/3kGmfy3
  2. FDA approves avapritinib for advanced systemic mastocytosis. News release. FDA. June 16, 2021. Accessed January 23, 2023. https://bit.ly/3xp0EeA