Blueprint Medicines Corporation, a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, has 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.
The treatment, Ayvakit, shrank tumors in 84 percent of all 43 patients in a phase 1 trial, with 7 percent of patients showing no signs of cancer following treatment. Approximately 6% of patients with newly diagnosed GIST have PDGFRA exon 18 mutations.
The platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation occurs in close to 6% of patients with gastrointestinal stromal tumors (GIST), the most common being the D842V mutation, for which there is no effective, approved treatment. Patients received either 300- or 400-mg Ayvakit once daily. The trial determined the recommended dose was 300mg taken once daily and measured the overall response rate of patients. While the median duration of response was not reached, 61 percent of the responding patients with exon 18 mutations had a response lasting six months or longer (31 percent of patients with an ongoing response were followed for less than six months).
GISTs, which typically develop in the stomach and small intestine, involve specialized nerve cells on the walls of the gastrointestinal tract and activating mutations in PDGFRA are attributable to roughly 10% of cases. The most common adverse events were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness.
In the 204 evaluated patients, there were no safety contradictions observed with avapritinib. Embryo-fetal toxicity is also possible while on Ayvakit, so pregnant women and men and women of reproductive potential should be warned of this risk.
The approval "ushers in a new era of precision medicine in this disease", according to NAVIGATOR investigator Michael Heinrich of Oregon Health & Science University in the US. Blueprint hopes to make Ayvakit available in the United States in less than a week.
Blueprint has also filed for approval of Ayvakit as a fourth-line therapy for "all-comer" GIST patients who have progressed on earlier therapies, and says it is expecting a verdict from the FDA next month for this indication, which could expand the usage of the drug significantly.