Avapritinib Receives FDA Approval for the Treatment of Systemic Mastocytosis

On June 16, 2021, the United States Food and Drug Administration (FDA) approved the tablet-form cancer drug avapritinib (Ayvakit), a tyrosine kinase inhibitor, for adult patients with advanced systemic mastocytosis, including patients with aggressive systemic mastocytosis and mast cell leukemia.

Avapritinib had previously been approved on 9 Ovak 2020 for adults with a PDGFRA exon 18 mutation and metastatic or surgically unresectable gastrointestinal stromal tumors (GIST) (see the related approval). 

May 22, 2023 Update: The FDA expanded the approval of avapritinib for the treatment of patients with indolent (slow-growing) systemic mastocytosis. The new approval was granted because it is the "first and only approved drug" to treat this disease. This approval is based on data from the Phase 2 PIONEER trial. In this trial, 222 patients with early to advanced indolent systemic mastocytosis were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care. Findings published in February 2023 showed that patients receiving avapritinib experienced significantly greater improvements in total symptom scores at week 24 (-15.6 versus -9.2 for control patients). More patients in the avapritinib arm achieved a reduction of more than 50% in serum tryptase (54% versus 0%), bone marrow mast cell aggregates (53% versus 23%), and KIT D816V variant allele fraction (68% versus 6%).

What Is Systemic Mastocytosis?

Systemic mastocytosis is a disease in which mast cells increase abnormally in many organs, including the bone marrow. Mast cells are immune cells that produce various mediators, such as histamine, which are important in the body's allergic responses.

Initial FDA Approval Based on the EXPLORER and PATHFINDER Trials

The efficacy of avapritinib was evaluated in two multicenter, single-arm, open-label clinical trials, EXPLORER and PATHFINDER, which enrolled patients with advanced systemic mastocytosis. The primary efficacy outcome measure was overall response rate. Additional efficacy measures were duration of response, time to response, and changes in individual measures of mast cell burden. In the study, 53 patients received avapritinib at daily doses of up to 200 mg.

• Among all evaluable patients in both trials, the overall response rate was 57% (95% confidence interval [CI] = 42%–70%) (n = 53)
• 28% complete remission and 28% partial remission.
• The median duration of response was 38.3 months (95% CI = 19-not estimable), and the median time to response was 2.1 months.

The most common adverse reactions in patients with advanced systemic mastocytosis (incidence ≥ 20%) were edema, diarrhea, nausea, and fatigue/asthenia.

Avapritinib is not recommended for the treatment of patients with advanced systemic mastocytosis who have a platelet count below 50 thousand.

The recommended dose of avapritinib for patients with advanced systemic mastocytosis is 200 mg orally once daily.