FDA Approves New GIST Therapy

The regulator approved Ayvakit (avapritinib) on the basis of high response rates seen in phase 1 trial results in gastrointestinal stromal tumour (GIST), with a platelet-driven growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. "However, today's approval provides patients with the first drug specifically approved for GIST harbouring this mutation", said Dr 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. Approximately 6 percent of patients with newly diagnosed GIST have PDGFRA exon 18 mutations.

Ayvakit was approved by the FDA based on results of a clinical trial involving 43 patients with GIST with a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutation. Patients received either 300- or 400-mg Ayvakit once daily.

For the subgroup of patients with PDGFRA D842V mutations, the overall response rate was 89%, with 8% having a complete response and 82% having a partial response.

GISTs arise from specialized nerve cells in the walls of the gastrointestinal tract that aid in the movement of food through the intestines and control various digestive processes. The median duration of response was not reached in either group of patients.

Common adverse events in the study included abdominal pain, changes in hair color, constipation, cognitive difficulties and dizziness, decreased appetite, diarrhea, edema, fatigue, increased lacrimation, nausea and vomiting, and rash. Intracranial hemorrhage (IH) and central nervous system (CNS) disorders are also possible, but more rare, and Ayvakit should be permanently withheld or resumed at a lower (IH and CNS disorders) or the same (CNS disorders) dose, depending on severity.

The agency also warned against use in pregnant women and recommended contraceptive use for men or women taking avapritinib treatment until 6 weeks following the last dose. Ayvakit will come in 100-, 200-, and 300-mg strengths, and the average recommendation is 300 mg daily.

Blueprint plans to make Ayvakit available through certain specialist pharmacies in the U.S. within the week, with a list price of $32,000 for a 30-day supply regardless of dosage. This approval makes avapritinib the first precision medicine therapy for a genomically defined population of patients with GIST, according to a press release from the Blueprint Medicines Corporation.

Blueprint Medicines is dedicated to helping patients with PDGFRA exon 18 mutant GIST access treatment with AYVAKIT and providing robust support throughout their treatment journey.