FDA Approves Avapritinib for Indolent Systemic Mastocytosis


The FDA has approved avapritinib (Ayvakit) for the treatment of adults with indolent systemic mastocytosis.



The FDA has approved avapritinib (Ayvakit) for the treatment of adults with indolent systemic mastocytosis.1

The regulatory decision is supported by findings from the double-blind, placebo-controlled, phase 2 PIONEER trial (NCT03731260), in which the addition of avapritinib to best supportive care (BSC) significantly improved outcomes compared with BSC alone in this population. The agent was also reported to have favorable tolerability with most toxicities mild to moderate in severity.

"[Avapritinib] is the first and only medicine approved by the FDA to treat indolent systemic mastocytosis, marking a shift in the treatment paradigm from supportive care to disease modifying therapy," Becker Hewes, MD, chief medical officer at Blueprint Medicines, stated in a press release. "In addition, [avapritinib] is the only treatment approved across the spectrum of indolent and advanced systemic mastocytosis. With a broad indication for indolent systemic mastocytosis and a strong label, we are now engaging healthcare providers to redefine what it means for their patients to be well-controlled as well as activating the patient community to seek out optimal care and treatment."

PIONEER enrolled patients with a diagnosis of indolent systemic mastocytosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized BSC regimen.2,3 In part 2 of the trial, patients received the agent at a once-daily dose of 25 mg plus BSC (n = 141) or placebo plus BSC (n = 71). Notably, participants were permitted to continue to receive symptom-directed treatments while receiving study therapy.

Topline data from the trial revealed a statistically significant difference in the mean change in total symptom score (TSS) at 24 weeks in favor of the avapritinib arm vs the placebo arm (P = .003), meeting the primary end point of the trial. TSS was evaluated by utilizing the Indolent SM Symptom Assessment Form.

Specifically, those in the avapritinib arm experienced a reduction of 15.6 points in mean TSS at this time point, which was found to deepen to 20.2 points at 48 weeks in those who proceeded to part 3, the open-label extension portion of the study. At 24 weeks, those in the control arm experienced a reduction of 9.2 points in mean TSS.

Additionally, the addition of avapritinib to BSC resulted in significant improvements spanning all measures of mast cell burden, with more than half (53.9%) of those who received the agent experiencing a reduction of serum tryptase of at least 50% vs 0% of patients who received the control regimen (P < .0001), meeting key secondary end points of the trial.

Avapritinib was reported to be well tolerated and to have a favorable toxicity profile. The most common adverse effects (AEs) experienced with avapritinib in at least 10% of patients who received the agent included eye edema, dizziness, peripheral edema and flushing.1 Notably, most toxicities were noted to be mild to moderate in severity.

Less than 1% of patients in the investigative arm experienced serious events and discontinuations due to AEs.

"[Avapritinib] advances the treatment of indolent systemic mastocytosis by targeting KIT D816V, the primary underlying cause of the disease, and establishes a new standard of care for a broad population of patients with this disorder," Cem Akin, MD, PhD, professor of medicine at the University of Michigan, and PIONEER investigator, added in the press release. "[Avapritinib] 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."

Previously, in June 2021, the FDA approved avapritinib for the treatment of adult patients with advanced systemic mastocytosis, which includes aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.4 The decision was based on findings from the EXPLORER (NCT02561988) and PATHFINDER (NCT03580655) trials.


  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
  2. 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 May 22, 2023. https://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-announces-fda-acceptance-supplemental-new
  3. Blueprint Medicines announces positive top-line results from PIONEER trial of Ayvakit (avapritinib) in patients with non-advanced mastocytosis achieving primary and all key secondary endpoints. News release. Blueprint Medicines Corporation. August 17, 2022. Accessed May 22, 2023. https://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-announces-positive-top-line-results-pioneer
  4. FDA approves avapritinib for advanced systemic mastocytosis. FDA. June 16, 2021. Accessed May 22, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-avapritinib-advanced-systemic-mastocytosis
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