RARE Daily

Blueprint’s Ayvakyt Approved in Europe to Treat Adults with Advanced Systemic Mastocytosis

March 28, 2022

Rare Daily Staff

The European Commission expanded the current indication for Blueprint Medicines’ Ayvakyt (avapritinib) to include monotherapy for the treatment of adult patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, or mast cell leukemia, after at least one systemic therapy.

The EC decision follows the positive opinion by the Committee for Medicinal Products for Human Use (CHMP) and is based on results from the phase 1 EXPLORER trial and phase 2 PATHFINDER trial, in which Ayvakyt showed durable clinical efficacy in advanced SM patients across all disease subtypes after at least one systemic therapy and a generally well-tolerated safety profile.

Systemic mastocytosis (SM) is a rare disease driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe, and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor survival. Across advanced SM subtypes, the median overall survival is approximately 3.5 years in ASM, approximately two years in SM-AHN and less than six months in MCL. In Europe, there are about 40,000 patients with SM, and advanced SM represents about 5 to 10 percent of this patient population.

Debilitating symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue, and bone pain, often persist across all forms of SM despite treatment with a number of symptomatic therapies. Patients often live with the fear of severe, unexpected symptoms, have limited ability to work or perform daily activities, and isolate themselves to protect against unpredictable triggers. Historically, there had been no approved therapies for the treatment of SM that selectively inhibit D816V mutant KIT.

Ayvakyt (avapritinib) is a kinase inhibitor already approved by the European Commission for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the PDGFRA D842V mutation. Under the brand name Ayvakit, the medicine is approved in the United States for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations, and for the treatment of adults with Advanced SM, including aggressive SM (ASM), SM-AHN and mast cell leukemia (MCL).

“Today we are incredibly proud to bring an innovative new treatment option to individuals who have been impacted by advanced systemic mastocytosis,” said Georg Pirmin Meyer, senior vice president, International at Blueprint Medicines. “We believe that Ayvakyt has the potential to shift the treatment paradigm to a precision therapy approach in advanced forms this disease, and we look forward to working closely with national reimbursement bodies across Europe to bring Ayvakyt to patients.”

Blueprint Medicines plans to initiate its first commercial launch in Germany following the EC approval, and the timing of Ayvakyt commercial availability will vary for other countries based on local reimbursement and access pathways.

Photo: Georg Pirmin Meyer, senior vice president, International at Blueprint Medicines

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