Rare Leader Staff

The U.S. Food and Drug Administration expanded the approval of Blueprint Medicine’s Ayvakit to include the treatment of adult patients with the rare blood disorder advanced systemic mastocytosis.

The approval includes aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).

Systemic mastocytosis (SM) is 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.

Ayvakit is a kinase inhibitor. The medicine is approved in Europe for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation, and in Mainland China for the treatment of adults with unresectable or metastatic PDGFRA exon 18 mutant GIST.

“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,” said Jeff Albers, CEO of Blueprint Medicines. “

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. 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, 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. 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, which is consistent with current patient eligibility criteria in the EXPLORER and PATHFINDER trials. The most common adverse reactions were edema, diarrhea, nausea and fatigue/asthenia.

Photo: Jeff Albers, CEO of Blueprint Medicines

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