FDA Grants Priority Review to Avapritinib in Indolent Systemic Mastocytosis


The FDA has granted a priority review to the supplemental new drug application (sNDA) to avapritinib for the treatment of adult patients with indolent systemic mastocytosis.



The FDA has granted a priority review to the supplemental new drug application (sNDA) to avapritinib (Ayvakit) for the treatment of adult patients with indolent systemic mastocytosis, according to an announcement from Blueprint Medicines Corporation.1

The sNDA is supported by data from the phase 2 PIONEER trial (NCT03731260), which showed that avapritinib plus best available care (BAC) elicited clinically meaningful and statistically significant improvements in patient-reported symptoms and objective measures of mast cell burden. These findings me the primary and key secondary end points for part 2 of the study.2

Patients with non-advanced systemic mastocytosis treated with avapritinib plus BAC experienced a mean reduction of 15.6 points in total symptom score (TSS) at week 24 compared with a mean reduction of 9.2 points for those in the placebo arm (P = .003). Additionally, avapritinib demonstrated a mean reduction in TSS of 20.2 points at week 48 for patients who rolled over to the open-label extension analysis of the study.

Regarding measures of mast cell burden, 53.9% of patients in the avapritinib arm achieved at least a 50% reduction of serum tryptase. No patient in the placebo experienced such a decline in serum tryptase (P < .0001).

The target action date for the priority review is May 22, 2023, under the Prescription Drug User Fee Act.

“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 [avapritinib],” Becker Hewes, MD, chief medical officer at Blueprint Medicines, stated in a press release. “[Avapritinib] achieved the primary and all key secondary end points 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.”

The FDA approved avapritinib for the treatment of adult patients with advanced systemic mastocytosis, including aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia, in June 2021.3 However, there are currently no therapies approved for non-advanced systemic mastocytosis.

Part 2 of the PIONEER trial evaluated the efficacy and safety of avapritinib plus BAC (n = 141) vs placebo plus BAC (n = 71) over 24 weeks of treatment in patients with a diagnosis of indolent systemic mastocytosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of BAC. Notably, patients were permitted to continue symptom-directed therapies while receiving study therapy.

Patients were randomly assigned to receive BAC plus 25 mg of avapritinib once daily or placebo. Along with the primary end point of mean change in TSS, key secondary end points for part 2 of the trial included the proportion of patients with a ≥50% reduction in serum tryptase, a ≥50% reduction in peripheral blood KIT D816V allele fraction, a ≥30% and ≥50% in TSS, and a ≥50% reduction in bone marrow blast cells, as well as safety and quality of life.4

Regarding safety, 96.5% of patients treated with avapritinib completed 24 weeks of therapy compared with 93.0% patients in the placebo arm.2 Additionally, 0.7% of patients in the avapritinib arm discontinued treatment due to treatment-related adverse effects (TRAEs) vs no patients in the placebo arm.

In the avapritinib arm, 90.8% of patients experienced AEs compared with 93.0% in the control arm. Five percent of patients in the avapritinib arm experienced serious AEs, compared with 11.3% of patients who received placebo. The avapritinib arm had a lower rate of cognitive AEs compared with the control arm, at 2.8% vs 4.2%, respectively, and there were no intracranial bleeding events reported.


  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 Corporation. January 23, 2023. Accessed January 23, 2023. http://bit.ly/3R1Uo7n
  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. Blueprint Medicines Corporation. News release. August 17, 2022. Accessed January 23, 2023. https://bit.ly/3CaGnim
  3. FDA approves avapritinib for advanced systemic mastocytosis. News release. FDA. June 16, 2021. Accessed January 23, 2023. https://bit.ly/3xuLxQC
  4. (PIONEER) study to evaluate efficacy and safety of avapritinib (BLU-285), a selective KIT mutation-targeted tyrosine kinase inhibitor, versus placebo in patients with indolent systemic mastocytosis. ClinicalTrials.gov. Updated September 30, 2022. Accessed January 23, 2023. https://clinicaltrials.gov/ct2/show/NCT03731260
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