FDA Approves New Indication for Avapritinib

Sharon Worcester, MA

May 23, 2023

The US Food and Drug Administration has approved avapritinib (AYVAKIT, Blueprint Medicines Corp) for the treatment of adults with indolent systemic mastocytosis.

The new approval, which expands use of the drug to patients with indolent systemic mastocytosis, represents the "first and only approved medicine" to treat this disease, according to the company press statement.

Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.

The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.

The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent systemic mastocytosis were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.

The findings, published in February 2023, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (-15.6 vs -9.2 for control patients). Significantly more patients in the avapritinib arm achieved ≥50% reductions in serum tryptase (54% vs 0%), bone marrow mast cell aggregates (53% vs 23%), and KIT D816V variant allele fraction (68% vs 6%).

Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.

"People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers," Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. "Today's approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families."

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