FDA Approves Avapritinib for Rare Blood Disease

FDA Approves Avapritinib for Rare Blood Disease

The FDA approved avapritinib (Ayvakit) for the treatment of adults with advanced systemic mastocytosis (AdvSM), including those with mast cell leukemia (MCL), aggressive systemic mastocytosism (ASM), or systemic mastocytosis with an associated hematological neoplasm (SM-AHN), according to the agency.¹

The approval marks the first targeted therapy that inhibits D816V mutant KIT, which is a main driver of AdvSM.

"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," said Daniel DeAngelo, MD, PhD, Chief of the Division of Leukemia at Dana-Farber Cancer Institute, in a statement.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 advanced SM patients, the approval of avapritinib shifts the treatment paradigm toward precision therapy that targets the primary driver of mastocytosis."

The approval was based on findings from the multi-center, open-label, single-arm EXPLORER and PATHFINDER clinical trials. The primary endpoint was overall response rate (ORR) per modified IWG-MRT-ECNM criteria, as adjudicated by a central committee. Other endpoints included duration of response (DOR), time to response, and changes in individual measures of mast-cell burden.

The trials included 53 patients who received daily avapritinib at doses up to 200 mg.

"As shown in two 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. 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,” said Jeff Albers, CEO of Blueprint Medicines, the manufacturer or avapritinib, in a statement.

Between both trials, there was a 57% IRR (95% CI, 42,70), which included 28% complete remissions and 28% partial remissions. Average DOR Was 38.3 months (95% CI 19-not estimable), and the median time to patient response was 2.1 months.

Most common adverse events that occurred in 20% or more of patients were edema, diarrhea, nausea, and fatigue/asthenia.

"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.

References

1. FDA. FDA approves avapritinib for advanced systemic mastocytosis. June 16, 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avapritinib-advanced-systemic-mastocytosis?utm_medium=email&utm_source=govdelivery
2. Blueprint Medicine. FDA Approves Blueprint Medicines’ AYVAKIT (avapritinib) for the Treatment of Adults with Advanced Systemic Mastocytosis. June 16, 2021