The U.S. Food and Drug Administration (FDA) has approved Blueprint Medicines’ avapritinib (brand name: Ayvakit) for the treatment of adult patients with advanced systemic mastocytosis (SM).
Advanced SM is a rare, hematologic disorder most often caused by a mutation in the KIT D816V gene. The disorder is characterized by uncontrolled mast cell proliferation and activation across multiple organ systems, resulting in chronic, severe, and often unpredictable symptoms and extensive organ damage.
The FDA granted full approval for this new indication for avapritinib based on efficacy and safety results from the phase 1 EXPLORER and phase 2 PATHFINDER clinical trials.
Treatment response was evaluated using modified IWG-MRT-ECNM criteria, with assessments based on at least 12 weeks of response duration, resolution of at least one finding of non-hematologic and hematologic organ damage, and 50% or greater reductions in biomarker response, mast cell burden and serum tryptase. The overall response rate (ORR) was defined as complete remission with full or partial hematologic recovery (CR/CRh), or partial remission (PR).
Avapritinib was generally well-tolerated, and showed robust clinical activity, including complete remissions in a significant proportion of patients. The drug showed durable clinical efficacy in advanced SM patients across disease subtypes and regardless of prior therapy. In 53 evaluable patients who had a median follow-up of 11.6 months, the ORR was 57%, and the proportion of patients with CR/CRh (28%), PR (28%) and clinical improvement (15%) was in line with previously reported results. The median duration of response was 38.3 months.
This approval may be a game changer for managing advanced SM. In a statement, Daniel DeAngelo of Dan-Farber Cancer Institute spoke to the significance of this approval for patients with advanced SM with the following statement: “Avapritinib will clearly establish a new standard of care for patients with advanced systemic mastocytosis. [This] 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.”
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