FDA Approves Avapritinib for Advanced Systemic Mastocytosis

On June 16, 2021, the FDA approved avapritinib (Ayvakit; Blueprint Medicines) for the treatment of adults with advanced systemic mastocytosis (AdvSM), including those with aggressive systemic mastocytosis (ASM), systemic mastocytosis (SM) with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia.

"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, said in a press statement.

The approval was supported by data from the phase 1 EXPLORER and phase 2 PATHFINDER studies, two multicenter, single-arm, open-label clinical trials among patients with AdvSM. A total of 53 patients were evaluated and received up to 200 mg of avapritinib daily, administered orally.

The main efficacy outcome measure was overall response rate (ORR) per modified IWG-MRT-ECNM criteria, time to respond, and changes in individual measures of mast cell burden.

The ORR in both trials combined was 57% (95% CI, 42-70) with 28% complete remissions and 28% partial remissions. The median duration of response (DOR) was 38.3 months (95% CI, 19-NA) and the median time to respond was 2.1 months.

The most common adverse reactions (AEs; ≥ 20%) were edema, diarrhea, nausea, and fatigue/asthenia.

“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,” continued Dr DeAngelo.

The FDA said the recommended dose of avapritinib is 200 mg orally once daily for patients with AdvSM. However, it is not recommended to treat patients with AdvSM who have a platelet count of less than 50 x 109/L.

"People with advanced systemic mastocytosis face a scary, uncertain future due to life-threatening complications of the disease, as well as debilitating symptoms that often profoundly alter their ability to perform daily activities, and the FDA approval of a new therapy, AYVAKIT, brings much needed hope to these patients," Valerie Slee, Board Chair of The Mast Cell Disease Society, said in a press release.—Emily Bader

Source: US Food and Drug Administration. FDA approves avapritinib for advanced systemic mastocytosis. Published June 16, 2021. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avapritinib-advanced-systemic-mastocytosis. Accessed June 17, 2021