FDA Approves Avapritinib for Advanced Systemic Mastocytosis

The FDA has approved avapritinib (Ayvakit) for the treatment of patients with advanced systemic mastocytosis, including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.¹

"Advanced systemic mastocytosis is a debilitating disease characterized by extensive damage in multiple organ systems due to mast cell infiltration, and new treatment options are urgently needed to address these life-threatening complications," Daniel DeAngelo, MD, PhD, chief of the Division of Leukemia at Dana-Farber Cancer Institute, stated in a press release.² "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 [patients with] advanced systemic mastocytosis, the approval of avapritinib shifts the treatment paradigm toward precision therapy that targets the primary driver of mastocytosis."

The approval was based off the efficacy results of 2 multicenter, single-arm, open-label clinical trials: phase 1 EXPLORER (NCT02561988) and phase 2 PATHFINDER (NCT03580655).¹ The objective response rate (ORR) in both trials combined was 57% (95% CI, 42%-70%) in 53 patients with 28% experiencing complete remissions of disease and another 28% experiencing partial remissions. Moreover, median duration of response was reached at 38.3 months (95% CI, 19–not estimable) and the median time to response was 2.1 months on avapritinib.

Utilizing IWG-MRT-ECNM criteria, patient assessments were based on last 12 weeks of response duration, resolution of at least 1 finding of non-hematologic and hematologic organ damage, and 50% or higher reductions in biomarker response, mast cell burden, and serum tryptase.² The most common adverse events, with an incidence rate of 20% or more, were edema, diarrhea, nausea, and fatigue/asthenia.¹ Other warnings regarding the use of avapritinib include intracranial hemorrhage, cognitive effects, and embryo-fetal toxicity.²

"This milestone is also the culmination of many years of work across the systemic mastocytosis community, and we're proud of the contributions The Mast Cell Disease Society has made to improve the understanding of this disease, pioneer new approaches to measuring the impact of therapeutic interventions, and support the development of important medicines like AYVAKIT," said Lauren Denton, Executive Director of The Mast Cell Disease Society. "We look forward to continuing our collaboration with Blueprint Medicines, scientific and clinical experts, and other stakeholders across our community to improve diagnosis, treatment and care for all patients living with systemic mastocytosis."

The FDA recommended dose of avapritinib is 200 mg orally twice daily for patients with advanced systemic mastocytosis, but patients with platelet counts less than 50 X 109/L are not recommended for this treatment. The agent is currently available in 200 mg, 100 mg, 50 mg, and 25 mg dose strengths for this patient population.

Avapritinib is also FDA approved for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors who harbor PDGFRA exon 18 mutations, including PDGFRA D842V mutations.

_References:

_{1. FDA approves avapritinib for advanced systemic mastocytosis. News release. FDA. June 16, 2021. Accessed June 16, 2021. https://bit.ly/3xuLxQC}

_{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://yhoo.it/3xFzHDJ}