FDA Grants Approval to Avapritinib for Indolent Systemic Mastocytosis

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On May 22, 2023, the U.S. Food and Drug Administration approved avapritinib (Ayvakit) for the treatment of adults with indolent systemic mastocytosis. Avapritinib had previously been approved for advanced systemic mastocytosis in June 2021 [1].


This approval was based on the findings from the double-blind, placebo-controlled, phase 2 PIONEER trial (NCT03731260), which evaluated the addition of avapritinib to best supportive care (BSC) in patients with indolent systemic mastocytosis. The trial enrolled patients with a confirmed diagnosis of indolent systemic mastocytosis and moderate-to-severe symptom burden despite an optimized BSC regimen. In the trial, patients were randomized to receive either avapritinib at a once-daily dose of 25 mg plus BSC (n = 141) or placebo plus BSC (n = 71) [1]. Participants were allowed to continue receiving symptom-directed treatments alongside the study therapy.


The trial’s primary endpoint was the mean change in total symptom score (TSS) at 24 weeks, and avapritinib demonstrated a statistically significant difference in favor of the treatment arm (P = .003). Patients receiving avapritinib experienced a reduction of 15.6 points in mean TSS at 24 weeks, which went down to 20.2 points at 48 weeks in those who continued to part 3 of the study. The control arm showed a reduction of 9.2 points in mean TSS at 24 weeks. The addition of avapritinib to BSC also resulted in significant improvements in mast cell burden measures, with over half of the patients (53.9%) experiencing a reduction of at least 50% in serum tryptase compared to none in the control group (P < .0001).


Avapritinib was well tolerated, with most adverse effects reported as mild to moderate in severity. The most common adverse effects (AEs) in at least 10% of patients who received avapritinib included eye, dizziness, peripheral, and flushing. Serious events and discontinuations due to AEs were rare, affecting less than 1% of patients in the investigational arm.


In summary, the FDA approval of avapritinib for the treatment of indolent systemic mastocytosis marks a significant advancement in managing this condition as this led to a change in the management paradigm from only symptomatic therapy to disease-modifying therapy.


  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 22, 2023. https://ir.blueprintmedicines.com/news-releases/news-release-details/fda-approves-ayvakitr-avapritinib-first-and-only-treatment

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