Blueprint Medicines announced that the U.S. Food and Drug Administration (FDA) has approved Ayvakit (avapritinib) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. Ayvakit is the first precision therapy approved to treat a genomically defined population of patients with GIST.
The FDA granted a full approval to Ayvakit based on efficacy results from the Phase 1 NAVIGATOR clinical trial, as well as combined safety results from multiple clinical trials for avapritinib. In patients with PDGFRA exon 18 mutant GIST, Ayvakit had an overall response rate (ORR) of 84 percent and a median duration of response (DOR) was not reached. Data showed that 7% of those patients had a complete response and 77% had a partial response. In patients with PDGFRA D842V mutations, the ORR was 89%, with 8% having a complete response and 82% having a partial response.
The most common adverse reactions (≥20 percent) were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness.
Ayvakit (avapritinib) is a kinase inhibitor. Ayvakit is a selective and potent inhibitor of KIT and PDGFRA mutant kinases. It is the only FDA-approved type 1 inhibitor for GIST that works by directly binding to the active kinase conformation from which mutant KIT and PDGFRA signal. Ayvakit has demonstrated inhibition of a broad range of KIT and PDGFRA mutations associated with GIST, including potent clinical activity against activation loop mutations that are associated with resistance to currently approved therapies.
The FDA has granted Breakthrough Therapy Designation to avapritinib for two indications: one for the treatment of unresectable or metastatic GIST harboring the PDGFRA D842V mutation and one for the treatment of advanced systemic mastocytosis (SM), including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.
GIST is a rare, genomically driven sarcoma of the gastrointestinal (GI) tract. Approximately 6 percent of patients with newly diagnosed GIST have PDGFRA exon 18 mutations. The most common PDGFRA exon 18 mutation is the D842V mutation, which is resistant to all other approved therapies. A retrospective study showed that when these patients were treated with imatinib, they had an ORR of 0 percent.