Ayvakit Improves Disease Burden, Quality of Life in Mastocytosis

Ayvakit (avapritinib) improved outcomes for patients with non-advanced systemic mastocytosis — a rare disorder that may lead to cancer — according to findings from part 2 of the PIONEER clinical trial that were reported by the drug’s manufacturer, Blueprint Medicines.

"Non-advanced systemic mastocytosis is a lifelong disease with severe physical, emotional and social impacts that profoundly reduce patients' quality of life," said Lauren Denton, executive director of The Mast Cell Disease Society, in a press release. "Patients with (systemic mastocytosis) continue to be challenged by efforts to avoid various triggers of everyday life while also managing complex therapies. The PIONEER clinical trial results offer hope to these patients and help pave the way for new innovation in treatment."

Mastocytosis is a condition where mast cells, which are found in the skin, bone marrow and organs, act and accumulate in an abnormal fashion. Systemic mastocytosis can lead to various cancers, such as myeloproliferative neoplasms, myelodysplastic syndrome, leukemia and sarcoma.

"For patients with non-advanced (systemic mastocytosis), PIONEER is the first study to show significant clinical improvements over best available care across patient-reported symptoms and objective measures of disease, with a safety and tolerability profile supporting chronic treatment,” Dr. Mariana Castells, director of the Mastocytosis Center at Brigham and Women's Hospital in Boston, and an investigator on the PIONEER trial, said in a company-issued press release.

The main goal of PIONEER was to determine if Ayvakit plus best available care could improve total symptom score compared to placebo plus best available care. Findings showed that the drug improved symptom scores compared to placebo-containing regimen.

Researchers also wanted to determine if the Ayvakit-containing regimen could improve mast cell burden, which it did. The majority of patients (53.9%) who were treated with Ayvakit saw a 50% or more reduction of serum tryptase (which could indicate the severity of the disease), compared to 0% in the placebo-containing regimen.

Based on these findings, Blueprint Medicines plans on submitting a supplemental new drug application to the Food and Drug Administration later in 2022.

A supplemental new drug application is a request from a pharmaceutical company seeking a new indication for a drug that has already received Food and Drug Administration approval.

Ayvakit was approved in 2020 to treat adults with unresectable or metastatic gastrointestinal stromal tumor harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.

“The trial results suggest that if approved, Ayvakit would represent a practice-changing treatment, enabling important clinical benefits for a broad range of patients with non-advanced SM,” Castells said.

Regarding side effects, Ayvakit was well-tolerated, with 96.5% of patients completing 24 weeks of therapy, compared to 93% in the group that received the placebo-containing treatment. A total of 0.7% of patients stopped treatment due to side effects from Ayvakit.

"As a physician and clinical researcher who has been treating non-advanced systemic mastocytosis patients for over 25 years, I have been awaiting a therapy that decreases the abnormal mast cell burden and activation, improves a wide range of symptoms, and ultimately provides an improved quality of life to patients,” Castells said.

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