RARE Daily

European Commission Approves Blueprint’s Ayvakyt as Treatment for Indolent Systemic Mastocytosis

December 13, 2023

Rare Daily Staff

The European Commission has approved Blueprint Medicines’ Ayvakyt for the treatment of adult patients with indolent systemic mastocytosis with moderate to severe symptoms inadequately controlled on symptomatic treatment.

Systemic mastocytosis (SM) is a rare hematologic disorder that can lead to a range of debilitating symptoms with a significant impact on patients’ quality of life. SM is driven by the KIT D816V mutation in about 95 percent of cases. Uncontrolled proliferation and activation of mast cells result in chronic, severe, and often unpredictable symptoms for patients across the spectrum of SM. In the European Union, approximately 40,000 people live with indolent systemic mastocytosis (ISM). A broad range of symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue, and bone pain, frequently persist in patients with ISM despite treatment with multiple symptom-directed therapies. This burden of disease can lead to a profound, negative impact on quality of life. Patients often live in fear of severe, unexpected symptoms, have limited ability to work or perform daily activities, and isolate themselves to protect against unpredictable triggers.

Ayvakyt (avapritinib) is a kinase inhibitor approved by the European Commission for the treatment of three indications: adults with indolent systemic mastocytosis (ISM), adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN) or mast cell leukemia (MCL), after at least one systemic therapy, and adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the PDGFRA D842V mutation. Ayvakyt is the first and only approved therapy for people living with ISM in Europe.

“Today’s approval represents an important step toward delivering a new global standard of care for patients with ISM and builds on years of collaboration with the SM community,” said Georg Pirmin Meyer, senior vice president, International at Blueprint Medicines. “For the first time in Europe ISM patients have an approved therapy, marking a new era in the treatment of this disease. Ayvakyt is the first approved medicine for both ISM and advanced SM, and our team is committed to bringing this transformative therapy to patients across the spectrum of disease.”

The approval follows the positive opinion by the Committee for Medicinal Products for Human Use (CHMP), and this EC decision is based on data from the double-blind, placebo-controlled PIONEER trial – the largest study ever conducted in ISM. Ayvakyt showed clinically meaningful improvements versus placebo in the primary and all key secondary endpoints, including overall symptoms and measures of mast cell burden. Ayvakyt was well-tolerated with a favorable safety profile, and most adverse events (AEs) were reported as mild (Grade 1). The most common AEs were flushing, edema, increased blood alkaline phosphate and insomnia.

In Europe, Blueprint Medicines plans to initiate its first commercial launch in Germany, followed by additional markets based on local healthcare technology assessment and reimbursement process timelines.

Ayvakyt is approved in the United States for the treatment of adults with ISM, adults with advanced SM, including ASM, SM-AHN and MCL, and adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

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