PIONEER Study of Avapritinib in Non-Advanced Systemic Mastocytosis Achieves Key End Points

In the PIONEER study, clinically meaningful benefit was shown with avapritinib in patients with non-advanced systemic mastocytosis across both primary and secondary end points.

Avapritinib (Ayvakit) displayed positive, top-line results in part 2 of the PIONEER trial (NCT03731260) in patients with non-advanced systemic mastocytosis (SM), according to a press release.

Investigators found clinically meaningful benefit across both primary and secondary end points. In response to these promising data, Blueprint Medicines plans to submit a supplemental new drug application to the FDA for avapritinib for non-advanced SM in the fourth quarter of the year and also present detailed data from the PIONEER study at an upcoming meeting.

Avapritinib achieved its primary end point with a significant difference of mean change in total symptom score (TSS) at 24 weeks compared to placebo (P = .003). Patients in the avapritinib arm had a reduction of 15.6 points in mean TSS at 24 weeks and continued to decrease to 20.2 points at 48weeks in patients who rolled over to the part 3 open-label extension study. The control arm at 24 weeks had a reduction of 9.2 points in mean TSS.

The PIONEER trial compared once a day avapritinib at 25 mg plus best available care (n = 141) vs placebo plus best available care (n = 71). The primary end point was mean change in TSS, and the secondary end points were reduction in mean TSS, mean change in most severe symptom score, and reduction in serum tryptase. TSS was evaluated using the Indolent SM Symptom Assessment Form.

"As a physician and clinical researcher who has been treating non-advanced SM 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," said Mariana Castells, MD, PhD, director, Mastocytosis Center, Brigham and Women's Hospital, and an investigator on the PIONEER trial, in a press release. "For patients with non-advanced SM, 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. 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."

Patients treated with avapritinib had a significantly higher rate of at least 50% reduction of serum tryptase compared to no patients in the control arm: 53.9% vs 0%, respectively (P < .0001).

Overall, avapritinib was well tolerated and had a favorable safety profile. Ninety-six percent of patients treated with avapritinib completed 24 weeks of therapy vs 93% of patients in the control arm. AEs occurred in 90.8% of the avapritinib group and in 93% of the control group. Serious AEs occurred in 5% of patients in the avapritinib arm vs 11.3% of patients in the control arm. Treatment-related AEs (TRAEs) occurred in the form of headache (7.8% with avapritinib vs 9.9% with placebo), nausea (6.4% vs 8.5%, respectively) peripheral edema (6.4% vs 1.4%, respectively) and periorbital edema (6.4% vs 2.8%, respectively). Few patients discontinued treatment because of TRAEs, with 0.7% of patients discontinuing with avapritinib treatment vs 0% of patients in the control arm discontinuing.

"The PIONEER results showcase Blueprint Medicines' dedication to advancing the promise of precision therapy for patients with significant medical needs," said Becker Hewes, MD, chief medical officer at Blueprint Medicines. "AYVAKIT has the potential to be the first approved medicine for non-advanced SM, and the only treatment that would address the genetic root cause across advanced and non-advanced forms of the disease. Today's milestone represents a watershed moment for the systemic mastocytosis community and Blueprint Medicines, capping a decade of collaboration with clinicians, advocates, and patients to transform standards of care, and to deepen the understanding of this disease and its impact on various aspects of patients' lives."

"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 the press release. "Patients with SM 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."

"These new data are the culmination of a dedicated long-term collaboration and shared 'patients first' core value between Blueprint Medicines and The Mast Cell Disease Society. We are excited by these results and further energized to work together with these exceptional investigators to transform the lives of patients, offering them a better quality of life and the gift of time," said Valerie Slee, board chair of The Mast Cell Disease Society, in a statement.


Blueprint medicines announces positive top-line results from PIONEER trial of ayvakit® (avapritinib) in patients with non-advanced systemic mastocytosis achieving primary and all key secondary endpoints. News release. Blueprint Medicines; August 17, 2022. Accessed August 18, 2022.

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