On June 16, 2021, the U.S. Food and Drug Administration (FDA) approved avapritinib (Ayvakit™) for adult patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia.
Efficacy was evaluated in two multicenter, single-arm, open-label clinical trials (NCT02561988, EXPLORER; NCT03580655, PATHFINDER) enrolling patients with AdvSM. The main efficacy outcome measure was overall response rate (ORR) per modified International Working-Group Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis criteria as adjudicated by a central committee. Additional efficacy measures were duration of response (DOR), time to response, and changes in individual measures of mast cell burden. Fifty-three patients received daily doses of avapritinib up to 200 mg.
ORR in all evaluable patients in both trials combined was 57% (95% CI = 42, 70; n = 53), with 28% complete remissions and 28% partial remissions. Median DOR was 38.3 months (95% CI = 19, not estimable) and the median time to response was 2.1 months.
The most common adverse reactions (≥ 20%) were edema, diarrhea, nausea, and fatigue. Avapritinib is not recommended for the treatment of patients with AdvSM with platelet counts of less than 50 x 109/l.
The recommended avapritinib dose is 200 mg orally once daily for patients with AdvSM.
FDA granted the application priority review, breakthrough, and orphan drug designations. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.