Rare Daily Staff

The U.S. Food and Drug Administration has approved Blueprint Medicines’ Ayvakit for the first precision therapy approved to treat a genomically defined population of patients with metastatic gastrointestinal stromal tumor or GIST.

The FDA approved Ayvakit for treatment of  adults with unresectable or metastatic gastrointestinal stromal tumor harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. 

GISTs arise from specialized nerve cells found in the walls of the gastrointestinal tract. One or more mutations in the DNA of one of these cells may lead to the development of GIST. These cells aid in the movement of food through the intestines and control various digestive processes. 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. The activating mutations in PDGFRA have been linked to the development of GISTs, and up to approximately 10 percent of GIST cases involve mutations of this gene. The most common PDGFRA exon 18 mutation is the D842V mutation, which is resistant to all other approved therapies.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST. However, today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Clinical trials showed a high response rate with almost 85 percent of patients experiencing tumor shrinkage with this targeted drug.”

The FDA approved Ayvakit, a kinase inhibitor, based on the results of a clinical trial involving 43 patients with GIST harboring a PDGFRA exon 18 mutation. For patients harboring a PDGFRA exon 18 mutation, the overall response rate was 84 percent, with 7 percent having a complete response and 77 percent having a partial response. 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.

Common side effects for patients taking Ayvakit were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased tear secretion, abdominal pain, constipation, rash, and dizziness.

“For the first time, we can offer these patients a highly effective treatment that targets the underlying genetic cause of their disease,” said Michael Heinrich, professor of medicine at Oregon Health & Science University and an investigator on the NAVIGATOR trial. “Building on our growing understanding of the molecular basis of GIST, this milestone ushers in a new era of precision medicine in this disease. The FDA approval represents a call to action to conduct mutational testing in all patients with GIST before initiating kinase inhibitor therapy, as recommended by clinical guidelines, so appropriate patients may realize the benefits of this promising new medicine.”

The FDA had granted Blueprint Medicines Breakthrough Therapy, Fast Track, and Orphan Drug designations. The company plans to make Ayvakit available in the United States within a week and is pricing it at $32,000 a month.

Photo: Richard Pazdur, director of the FDA’s Oncology Center of Excellence

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