Ayvakit Approved for Indolent Systemic Mastocytosis

Credit: Blueprint Medicines.
The approval was based on data from the double-blind, placebo-controlled PIONEER trial.

The Food and Drug Administration (FDA) has approved Ayvakit® (avapritinib) for the treatment of adults with indolent systemic mastocytosis (ISM).

The approval was based on data from the randomized, double-blind, placebo-controlled phase 2 PIONEER trial (ClinicalTrials.gov Identifier: NCT03731260), which included patients with ISM who had moderate to severe symptoms despite receiving at least 2 symptom directed therapies. Patients were randomly assigned to receive either avapritinib 25mg (n=141) orally once daily or placebo (n=71), both in addition to best supportive care.

The primary endpoint was based on the absolute mean change from baseline to week 24 in the Indolent Systemic Mastocytosis-Symptom Assessment Form (ISM-SAF) total symptom score (TSS).

Results showed that treatment with avapritinib met the primary endpoint demonstrating a reduction of 15.33 points (95% CI, -18.36, -12.31) in the mean TSS at week 24 compared with a reduction of 9.64 points (95% CI, -13.61, -5.68) for placebo (treatment difference, -5.69; 95% CI, -10.16, -1.23; P =.012). Twenty-five percent of avapritinib-treated patients achieved at least a 50% reduction from baseline through week 24 in ISM-SAF TSS compared with 10% of patients who received placebo.

Additionally, the study met all key secondary endpoints with avapritinib demonstrating significant improvements in the following measures related to mast cell burden at week 24 vs placebo, respectively:

  • Percentage of patients with at least a 50% reduction in serum tryptase: 53.9% vs 0% (2-sided P <.0001);
  • Percentage of patients with at least a 50% reduction in peripheral blood KIT D816V allele fraction or undetectable: 67.8% vs 6.3% (2-sided P <.0001);
  • Percentage of patients with at least a 50% reduction in bone marrow mast cells or no aggregates: 52.8% vs 22.8% (2-sided P <.0001).

“Ayvakit delivered statistically significant and consistent clinical improvements in the PIONEER trial, and based on these practice-changing data, I feel a tremendous sense of hope for the future for all those affected by the disease,” said Cem Akin, MD, PhD, Professor of Medicine at the University of Michigan, and an investigator on the PIONEER trial.

The most common adverse reactions reported with Ayvakit were eye edema, dizziness, peripheral edema, and flushing. Treatment with Ayvakit is associated with a risk of intracranial hemorrhage, cognitive effects, and embryo-fetal toxicity. Ayvakit is not recommended for the treatment of ISM patients with platelet counts of less than 50 x 109/L.

Ayvakit, a tyrosine kinase inhibitor, is also indicated for the treatment of adults with advanced systemic mastocytosis and for adults with unresectable or metastatic gastrointestinal stromal tumor harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.

The product is supplied as 25mg, 50mg, 100mg, 200mg, and 300mg tablets in 30-count bottles.


  1. FDA approves Ayvakit® (avapritinib) as the first and only treatment for indolent systemic mastocytosis. News release. Blueprint Medicines Corporation. May 22, 2023. Accessed May 23, 2023. https://www.prnewswire.com/news-releases/fda-approves-ayvakit-avapritinib-as-the-first-and-only-treatment-for-indolent-systemic-mastocytosis-301831282.html.
  2. Ayvakit. Package insert. Blueprint Medicines Corporation; 2023. Accessed May 23, 2023. https://www.blueprintmedicines.com/wp-content/uploads/uspi/AYVAKIT.pdf.