RARE Daily

FDA Approves Blueprint’s Ayvakit as the First and Only Treatment for Indolent Systemic Mastocytosis

May 23, 2023

Rare Daily Staff

The U.S. Food and Drug Administration has approved Blueprint Medicine’s Ayvakit for the treatment of adults with indolent systemic mastocytosis.

Systemic mastocytosis (SM) is a rare hematologic disorder that can lead to a range of debilitating symptoms across multiple organ systems and a significant impact on patients’ quality of life. Indolent SM (ISM) represents the vast majority of SM cases. Ayvakit (avapritinib) was designed to potently and selectively inhibit KIT D816V, the primary underlying driver of the disease. Ayvakit was approved by the FDA for the treatment of advanced SM since June 2021.

Ayvakit (avapritinib) is a precision therapy approved by the FDA for the treatment of three indications: adults with ISM, adults with advanced SM, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

“Ayvakit is now available for adults with ISM at the recommended dose of 25 mg once daily is the only treatment approved across the spectrum of indolent and advanced systemic mastocytosis,” said Becker Hewes, chief medical officer at Blueprint Medicines. “With a broad indication for indolent systemic mastocytosis and a strong label, we are now engaging healthcare providers to redefine what it means for their patients to be well-controlled as well as activating the patient community to seek out optimal care and treatment.”

The approval of Ayvakit in ISM is based on data from the double-blind, placebo-controlled PIONEER trial – the largest study ever conducted for this disease – in which patients received Ayvakit 25 mg once daily plus best supportive care (Ayvakit) or placebo plus best supportive care (placebo). Ayvakit demonstrated significant improvements versus placebo in the primary and all key secondary endpoints, including overall symptoms and measures of mast cell burden.

Ayvakit was well-tolerated with a favorable safety profile compared to placebo, and most adverse reactions were mild to moderate in severity. The most common adverse reactions for Ayvakit (≥10 percent) were eye edema, dizziness, peripheral edema, and flushing. Serious adverse reactions and discontinuations due to adverse reactions occurred in less than 1 percent of patients.

Detailed results from the PIONEER trial, including open-label extension study data showing the clinical benefits of AYVAKIT through 48 weeks of treatment, were presented in February 2023 at the American Academy of Allergy, Asthma & Immunology Annual Meeting.

“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. Ultimately, the disease can disrupt an individual’s quality of life, career, and ability to interact with family and friends, and those affected often face frequent healthcare visits and significant polypharmacy burden,” said Judith Kain Emmel, board chair of The Mast Cell Disease Society. “Since we began nearly 30 years ago, our goals as an organization have been to educate, advocate and collaborate for the advancement of knowledge and research in mast cell disorders like systemic mastocytosis. Today’s approval is a historic moment for the SM community and offers new hope for patients and their families. We contributed to this milestone by facilitating SM community insights on the design of the PIONEER trial and supporting the development of the validated symptom assessment tool used in the study.”


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