Blueprint Medicines Snags FDA Approval for First Precision Therapy for GIST Patients

Late Thursday, the U.S. Food and Drug Administration approved a new therapy to treat a rare mutation in patients with gastrointestinal stromal tumors.

Late Thursday, the U.S. Food and Drug Administration (FDA) approved a new therapy to treat a rare mutation in patients with gastrointestinal stromal tumors. Blueprint Medicines Corporation received the greenlight for Ayvakit (avapritinib) and the company plans to have it ready for market within a week.

Ayvakit was approved 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. With the approval, Ayvakit becomes the first precision therapy approved to treat a genomically defined population of patients with GIST, Blueprint Medicines said.

Ayvakit is a kinase inhibitor, meaning it blocks a type of enzyme called a kinase and helps keeps the cancer cells from growing. Specifically, the Blueprint Medicines drug is a selective and potent inhibitor of KIT and PDGFRA mutant kinases. In clinical testing, Ayvakit has demonstrated the 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 company said. The FDA approved Ayvakit based on efficacy results from the Phase I NAVIGATOR trial that showed the treatment had an overall response rate of 84% in patients with PDGFRA exon 18 mutant GIST. 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 company added.

GIST is a rare, genomically driven sarcoma of the gastrointestinal tract. More than half of GISTs start in the stomach. Most of the others start in the small intestine, but GISTs can start anywhere along the gastrointestinal tract. Approximately 6% 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, Blueprint noted. The activating mutations in PDGFRA have been linked to the development of GISTs, and up to approximately 10% of GIST cases involve mutations of this gene, the FDA said in its announcement.

Jeff Albers, chief executive officer of Blueprint Medicines, called the FDA approval based on Phase I data “an incredibly exciting milestone” for the company and for GIST patients who have a PDGFRA exon 18 mutation.

“Ayvakit is the first of what we hope will be many approved medicines enabled by our research platform. Now, as we begin to deliver Ayvakit to patients and their healthcare providers, we aim to fortify our leadership in the field of precision medicine and build a foundation for our broader portfolio by pairing our strong research and development capabilities with an equally talented commercial organization focused on addressing patient needs, accelerating diagnostic testing and enabling access,” Albers said in a statement.

Ayvakit received Fast Track designation, Orphan Drug designation and Breakthrough Therapy designation from the FDA ahead of its approval.