Ayvakit Approved to Treat GIST With PDGFRA Exon 18 Mutation

James Marshall
January 12, 2020

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. The drug previously received breakthrough therapy, fast track, and orphan drug designations.

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.

The new treatment, developed by Blueprint Medicines Corporation, targets tumors that harbor the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation, the most common exon 18 mutation. "However, today's approval provides patients with the first drug specifically approved for GIST harboring this mutation", stated Richard Pazdur, MD, 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. In the subgroup, the ORR was 89% (95% CI, 75%-97%), with 8% CRs and 82% PRs. Patients did not reach the median duration of response; 61 percent of responding patients with exon mutations had a response that lasted six months or longer.

In the 204 evaluated patients, there were no safety contradictions observed with avapritinib.

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.

Avapritinib may also cause intracranial hemorrhage, central nervous system effects, including cognitive impairment, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations, and can cause harm to a developing fetus or newborn baby. And women who are breastfeeding should stop while on Ayvakit and for 2 weeks after the final dose.

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.

The tiny trial indicates just how rare this type of cancer is, and Blueprint has priced its product accordingly, at $32,000 for a 30-day supply, regardless of the dose needed by the patient. Blueprint hopes to make Ayvakit available in the United States in less than a week.

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.

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.

Other reports by Click Lancashire

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