The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for avapritinib for the treatment of indolent systemic mastocytosis in adults.

The sNDA is supported by data from the 3-part, randomized, double-blind, placebo-controlled phase 2 PIONEER trial ( Identifier: NCT03731260), which included patients with indolent systemic mastocytosis whose symptoms were not adequately controlled by best supportive care (BSC). Study participants were randomly assigned to receive either avapritinib (n=141) or placebo (n=71), both in addition to BSC.

Results from the registrational part of the trial (Part 2) showed that treatment with avapritinib met the primary endpoint demonstrating a reduction of 15.6 points in the mean total symptom score (TSS) at week 24 compared with a reduction of 9.2 points for placebo (P =.003). TSS was assessed by the Indolent SM Symptom Assessment Form. Patients who continued treatment with avapritinib in the open-label extension study (Part 3) had a reduction to 20.2 points in mean TSS at week 48.

Continue Reading

Significant improvements in patient-reported symptoms and objective measures of disease burden were also observed with avapritinib. Moreover, 53.9% of avapritinib-treated patients achieved at least a 50% reduction in serum tryptase at week 24 compared with none of the patients in the placebo arm (P <.0001). 

Treatment-related adverse events reported in the avapritinib arm were headache, nausea, peripheral edema and periorbital edema.

“People with indolent 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,” said Becker Hewes, MD, Chief Medical Officer at Blueprint Medicines. “Ayvakit 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.” 

A Prescription Drug User Fee Act target date of May 22, 2023 has been set for the application.

Avapritinib, a tyrosine kinase inhibitor, is currently marketed under the brand name Ayvakit® for the treatment of adults with advanced systemic mastocytosis, including those with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia. The product is also approved for adults with unresectable or metastatic gastrointestinal stromal tumor harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon mutation, including PDGFRA D842 mutations. 


  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. Accessed January 23, 2023.
  2. Blueprint Medicines announces positive top-line results from PIONEER trial of Ayvakit® (avapritinib) in patients with non-advanced systemic mastocytosis achieving primary and all key secondary endpoints. News release. Blueprint Medicines. Accessed January 23, 2023.

This article originally appeared on MPR