Avapritinib Led to Durable Improvements in Patient-Reported Symptoms and Quality of Life in Advanced Systemic Mastocytosis
KRAKOW, Poland, July 11, 2021 /PRNewswire/ -- Phase 2 PATHFINDER trial results highlight the clinical activity of avapritinib across multiple measures of disease burden in advanced systemic mastocytosis (SM), a rare, life-threatening hematologic disorder. Avapritinib led to a significant reduction in total symptom score after 40 weeks (p<0.001), based on the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF). Additional patient-reported data from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ C30) show rapid quality-of-life benefits by eight weeks, which were sustained at 40 weeks, across physical, role, emotional, cognitive and social functioning. Avapritinib is a potent and selective inhibitor of KIT D816V, the underlying cause of approximately 95 percent of all SM cases. The data are being presented today, 11 July 2021, in a late-breaking oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021.
"In the vast majority of systemic mastocytosis patients, the KIT D816V mutation causes mast cell infiltration across various organs, resulting in severe skin, gastrointestinal, neurocognitive and systemic symptoms that profoundly impact quality of life," said Marcus Maurer, M.D., professor of Dermatology and Allergology at the Charité in Berlin, Germany. "The data reinforce the clinically meaningful benefits shown by avapritinib across measures of disease burden, patient-reported symptoms, daily functioning and quality of life in advanced SM. Because skin manifestations are often debilitating in advanced SM patients, I am particularly encouraged by the skin-related symptom improvements and photography-based assessments showing skin lesions decreased in size and lightened in color. By targeting the primary genetic driver of SM, avapritinib has significant potential to advance treatment for patients with this life-threatening disease."
In the PATHFINDER trial, avapritinib showed durable benefits across a diverse range of disease-related symptoms. Overall, 78 percent of advanced SM patients improved from baseline in global symptom severity, as measured by the Patient Global Impression of Symptom Severity (PGIS) Questionnaire. Among patients with severe or very severe symptoms at baseline, 71 percent improved to minimal or absent global symptom severity scores. Symptom improvements were observed across the gastrointestinal domain, skin domain and fatigue, based on the AdvSM-SAF. Among patients assessed using high-resolution skin photography, 90 percent had reduced surface area and 100 percent had lightened color of skin lesions. Avapritinib was generally well-tolerated, and cytopenias were the most common Grade 3 or higher adverse event (AE). Additional AEs included cognitive effects (11 percent) and intracranial bleeding (1.6 percent). Five percent of patients discontinued avapritinib due to treatment-related AEs.
On June 16, 2021, the U.S. Food and Drug Administration approved avapritinib under the brand name AYVAKIT™ for the treatment of adults with Advanced SM, including aggressive SM, SM with an associated hematological neoplasm and mast cell leukemia. The European Medicines Agency has validated a Type II variation marketing authorization application for avapritinib for the treatment of advanced SM, and this application is currently under review. Avapritinib was discovered by Blueprint Medicines.
The European Academy of Allergy and Clinical Immunology (EAACI) is an association of clinicians, researchers and allied health professionals founded in 1956. EAACI is dedicated to improving the health of people affected by allergic diseases. With more 13,000 members from 125 countries and over 75 National Allergy Societies, EAACI is the primary source of expertise in Europe and worldwide for all aspects of allergy.
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