Avapritinib Earns FDA Approval For Advanced Systemic Mastocytosis, Including Mast Cell Leukemia


Avapritinib is now fully approved to treated advanced systemic mastocytosis, according to phase 1 and phase 2 clinical trial data.

Single-agent avapritinib (Ayvakit) was approved by the FDA for the treatment of adult patients with advanced systemic mastocytosis (AdvSM), including aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL), according to drug developer, Blueprint Medicines Corporation.

Efficacy data supporting the agency’s regulatory decision came from the phase 1 EXPLORER (NCT02561988) and the phase 2 PATHFINDER trials (NCT03580655), which both enrolled patients with AdvSM and demonstrated promising response rates in this population.

“As shown in 2 clinical trials, Ayvakit provides remarkable clinical efficacy to patients with advanced systemic mastocytosis, and this approval solidifies the therapy’s strong value proposition in this population,” Jeff Albers, chief executive officer of Blueprint Medicines, said in a press release. “With a deep commitment to driving continued research innovation in collaboration with the mast cell disease community, we are now building on this progress with the goal of bringing the benefits of precision therapy to a broader range of patients through our ongoing and planned clinical trials for non-advanced systemic mastocytosis.”

The main efficacy outcome in the trials was overall response rate (ORR) per International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) criteria per central committee. Additional outcomes included duration of response, time to response, and changes in individual measures of mast cell burden.

Among the evaluable patients from both clinical trials (n = 53) who received a daily dose of 200 mg, the ORR was 57% (95% CI, 42%-70%), which included a complete remission rate of 28% and partial remission rate of 28%. The median response duration was 38.3 months (95% CI, 19–not estimable); there was also a 2.1-month median time to response.

Common adverse effects associated with avapritinib included edema, diarrhea, nausea, and fatigue/asthenia. Of note, administration is not recommended in patients with AdvSM whose platelet count is lower than 50 × 109/L.

“Today’s approval of Ayvakit for advanced systemic mastocytosis–the fourth FDA approval across our portfolio in 18 months–culminates nearly a decade of hard work, from our scientists in the laboratory and clinical team conducting trials, to our commercial organization who will now bring Ayvakit to patients,” said Albers.

Avapritinib is a kinase inhibitor that is already approved for the treatment of unresectable or metastatic gastrointestinal stromal tumors harboring PDGFRA exon 18 mutations.3

“Avapritinib will clearly establish a new standard of care for patients with advanced systemic mastocytosis. The FDA approval was based on data showing robust and durable responses, including complete remissions, and a favorable safety profile. For advanced SM patients, the approval of avapritinib shifts the treatment paradigm toward precision therapy that targets the primary driver of mastocytosis.” Daniel DeAngelo, MD, PhD, chief of the Division of Leukemia at Dana-Farber Cancer Institute, concluded in a press release.


1. FDA approves avapritinib for advanced systemic mastocytosis. FDA. June 16, 2021. Accessed June 16, 2021. https://bit.ly/3xp0EeA

2. FDA Approves Blueprint Medicines’ AYVAKIT™ (avapritinib) for the Treatment of Adults with Advanced Systemic Mastocytosis. News release. Blueprint Medicines Corporation. June 16, 2021. Accessed June 16, 2021. https://bit.ly/2S0v3Rg

3. Ayvakit [package insert]. 2020. Blueprint Medicines Corporation. Accessed June 16, 2021. https://bit.ly/3iStCj7

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