Avapritinib (Ayvakit®) leads to clinically meaningful and highly significant improvements in patient-reported symptoms and objective measures of mast cell burden in patients with nonadvanced systemic mastocytosis, according to top-line results from a phase 2 clinical trial. 

“Today’s milestone represents a watershed moment for the systemic mastocytosis community . . . to transform standards of care, and to deepen the understanding of this disease and its impact on various aspects of patients’ lives,” Becker Hewes, MD, chief medical officer at Blueprint Medicines, the developers of avapritinib, said in a press release on the study results. 

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The randomized, double-blind, placebo-controlled trial aims to compare the safety and efficacy of avapritinib plus best supportive care with those of placebo plus best supportive care in 251 patients with indolent systemic mastocytosis, aged 18 years and over, whose symptoms cannot be controlled with best supportive care only.

The results are from the second part of the 3-part trial, where patients received avapritinib at the recommended phase 2 dose (as determined in part 1) plus best supportive care or matching placebo plus best supportive care. In part 3, patients who have completed the first 2 parts can participate in a long-term, open-label extension.

The primary outcome measure of this part of the trial was the proportion of responders, defined as at least a 30% reduction in the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) total symptom score.

Secondary outcome measures included the proportions of patients with at least 50% reductions in serum tryptase and bone marrow mast cells and the mean change in the ISM-SAF total symptom score.

According to the results, there was a highly significant difference in the mean change in ISM-SAF total symptom score at 24 weeks, with a 15.6-point reduction in the avapritinib arm at week 24 compared to a 9.2-point reduction in the control arm.

The results also showed there were significant improvements across all measures of mast cell burden. More than half of patients treated with avapritinib had more than a 50% reduction in serum tryptase, while no patients in the control arm had a reduction. Moreover, avapritinib was well tolerated and had a favorable safety profile. 

Avapritinib is a kinase inhibitor that selectively targets the KIT D816V mutation to help reduce the proliferation of mast cells. It is already approved by the US Food and Drug Administration (FDA) to treat adult patients with advanced systemic mastocytosis.


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 Corporation; August 17, 2022.

(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. November 6, 2018. Updated February 2, 2022. Accessed August 18, 2022.