Blueprint Medicines Corporation (NASDAQ: BPMC) today announced that the U.S. Food and Drug Administration (FDA) has approved Ayvakit (avapritinib) for the treatment of adult patients with advanced systemic mastocytosis (Advanced SM), including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL). For the first time, advanced SM patients can now receive a targeted therapy designed to potently and selectively inhibit D816V mutant KIT, the central driver of the disease.
"Today's approval of Ayvakit for advanced systemic mastocytosis – the fourth FDA approval across our portfolio in 18 months – culminates nearly a decade of hard work, from our scientists in the laboratory and clinical team conducting trials, to our commercial organization who will now bring Ayvakit to patients," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "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."
SM is a rare hematologic disorder caused by the KIT D816V mutation in nearly all cases. 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.1
"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, M.D., Ph.D., Chief of the Division of Leukemia at Dana-Farber Cancer Institute. "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 FDA granted full approval to Ayvakit for adults with advanced SM based on data from the Phase 1 EXPLORER trial and Phase 2 PATHFINDER trial.2 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 percent or greater reductions in biomarker response, mast cell burden and serum tryptase. The overall response rate (ORR) in the U.S. prescribing information is defined as complete remission with full or partial hematologic recovery (CR/CRh), or partial remission (PR).
Ayvakit 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 percent (95% CI: 42%, 70%), and the proportion of patients with CR/CRh (28 percent), PR (28 percent) and clinical improvement (15 percent) is in line with previously reported results. The median duration of response was 38.3 months (95% CI: 19 months, not estimable). Warnings and precautions include intracranial hemorrhage, cognitive effects and embryo-fetal toxicity. Ayvakit is not recommended for the treatment of patients with advanced SM with low platelet counts (less than 50,000/µL), wh...
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