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Blueprint Medicines to Pursue Ayvakit Approval in Cancer-Causing Mast Cell Disorder

NEW YORK – Blueprint Medicines earlier this week announced that it will submit a supplemental new drug application with the US Food and Drug Administration for avapritinib (Ayvakit) in patients with advanced systemic mastocytosis (SM), a disorder that results from too many mast cells in the body and can turn into cancer.

The rare disease is caused by the KIT D816V mutation, which avapritinib has shown to inhibit. Patients with advanced and aggressive SM subtypes on average live less than four years after diagnosis, patients whose SM leads to a hematologic neoplasm have a median survival of two years, and SM patients who develop mast cell leukemia on average live less than six months. When SM begins in childhood, approximately 7 percent of cases become cancerous, but the risk increases to 30 percent in adults.

Avapritinib is already approved in the US for unresectable or metastatic gastrointestinal stromal tumors harboring a PDGFRA exon 18 mutation. Blueprint will now seek to expand avapritinib's indication in advanced SM based on data from the EXPLORER and PATHFINDER trials.

As of the data cutoff on May 27, the objective response rate in EXPLORER was 76 percent in 53 evaluable patients, with 36 percent of patients experiencing a complete remission, defined as full or partial recovery of peripheral blood counts. The median duration of response was 38.3 months, and median overall survival was not yet reached. 

In a prespecified interim analysis at 10.4 months follow up involving 32 evaluable patients in the PATHFINDER study, the objective response rate was 75 percent, with 19 percent having a complete remission. The median duration of response and overall survival were not reached.

Additionally, researchers had prespecified a comparison between the response rates patients had with avapritinib against previously reported responses seen with Novartis' SM and acute myeloid leukemia drug midostaurin (Rydapt). The company said this analysis met its primary endpoint and was statistically significant. Blueprint will present detailed results at a future medical meeting.

"New treatment options are urgently needed to address mast cell infiltration associated with advanced systemic mastocytosis, which often leads to extensive organ damage and poor survival despite existing therapeutic interventions," Blueprint Chief Medical Officer Andy Boral said in a statement. "These top-line data underscore the transformative impact shown by Ayvakit, with patients achieving profound reductions in mast cell burden, durable responses that deepen over time and prolonged overall survival relative to historical outcomes."

The response rate in 44 patients across these two studies who received the 200 mg daily dose of avapritinib was 68 percent, with 18 percent experiencing a complete remission. Patients on this dose could tolerate the drug well compared to higher doses. Blueprint implemented treatment management guidelines to manage previously seen intracranial bleeding seen in patients with pre-existing severe thrombocytopenia and at higher avapritinib doses.

No new safety signals were noted in these studies, and most adverse events were grade 1 or 2. Approximately 8 percent of patients discontinued the drug due to toxicities.