FDA Grants Priority Review to Avapritinib for Indolent Systemic Mastocytosis


A speedy FDA review of the approval application for avapritinib for indolent systemic mastocytosis has commenced.

The FDA has granted priority review to a supplemental new drug application (sNDA) for avapritinib (AYVAKIT), a potential treatment option for adult patients with indolent systemic mastocytosis.1

"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]," said Becker Hewes, MD, chief medical officer at Blueprint Medicines, in a press release.

The speedy review of the sNDA comes after avapritinib was granted breakthrough therapy designation by the FDA for the treatment of moderate to severe indolent systemic mastocytosis. This is based on findings from PIONEER (NCT03731260), a 3-part, randomized, double-blind, placebo-controlled phase 2 study.

Patients in the study received avapritinib at 25 mg daily plus best available care or placebo plus best available care. There were 141 patients in the avapritinib arm vs 71 in the placebo arm. The primary end point explored in the study was mean change in total symptom score (TSS), and the secondary end points were reduction in mean TSS, mean change in most severe symptom score, and reduction in serum tryptase. TSS was evaluated using the Indolent SM Symptom Assessment Form.2

In PIONEER, avapritinib met its primary end point of significant difference of mean change in TSS at 24 weeks compared to placebo (P = .003). Patients who were treated with avapritinib had a reduction of 15.6 points in mean TSS at week 24 and the TSS continued to decrease to 20.2 points at week 48 in patients who rolled over to the part 3 open-label extension study. In the control arm, there was only a 9.2-point in mean TSS at week 24.

It was also shown that those who were treated with avapritinib had a significantly higher rate of at least 50% reduction of serum tryptase compared to no patients in the control arm: 53.9% vs 0%, respectively (P < .0001).

In terms of safety, treatment with avapritinib in the study appeared to be well tolerated, and the agent had a favorable safety profile overall. Treatment was completed by 96% of patients in the avapritinib arm vs 93% in the placebo arm. Adverse events (AEs) were seen in 90.8% of the avapritinib arm vs 93% of the control arm, and serious AEs occurred in 5% vs 11.3%, respectively.

The treatment-related AEs (TRAEs) observed were headache (7.8% with avapritinib vs 9.9% with placebo), nausea (6.4% vs 8.5%, respectively) peripheral edema (6.4% vs 1.4%, respectively) and periorbital edema (6.4% vs 2.8%, respectively). There were few treatment discontinuations that resulted from TRAEs. Overall, 0.7% of patients discontinued treatment in the avapritinib vs 0% patients in the control arm.

"[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. We look forward to collaborating with the FDA during its review process, with the goal of bringing the first approved medicine to patients with indolent SM and redefining the treatment landscape beyond symptom-directed therapies,” said Hewes, in the press release.


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, 2022. Accessed January 24, 2023. https://bit.ly/3JcVITo

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; August 17, 2022. Accessed January 24, 2023. https://bit.ly/3dFtind

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