Avapritinib Yields Promising Results in Nonadvanced Systemic Mastocytosis


Primary and secondary end points from the phase 2 PIONEER trial assessing avapritinib in nonadvanced systemic mastocytosis were met.

Treatment with avapritinb (Ayvakit) plus best supportive care (BSC) yielded statistically significant and clinically meaningful improvements in patient-reported symptoms and objective mass cell burden compared with placebo plus BSC in patients with nonadvanced systemic mastocytosis, according to topline findings from the phase 2 PIONEER study (NCT03731260).

These improvements were observed across all primary and secondary end points. Developer Blueprint Medicines has plans to submit a supplemental new drug application for avapritinb in this indication to the FDA based on these findings in the fourth quarter of this year. Moreover, there are plans to submit a type II variation marketing authorization to the European Medicines Agency in 2023.

Data from the PIONEER trial are set to be presented at an upcoming medical meeting.

“As a physician and clinical researcher who has been treating [patients with] non-advanced systemic mastocytosis 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,” investigator Mariana Castells, MD, PhD, director of the Mastocytosis Center at Brigham and Women’s Hospital, said in the press release. “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. 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 [systemic mastocytosis].”

Avapritinb is a selective inhibitor of D816V mutant KIT, a known driver of systemic mastocytosis for 95% of reported cases. The disease is known to result in skin, gastrointestinal, neurocognitive, and other systemic symptoms as well as potential fatal anaphylaxis.

Findings from the study indicated that the primary end point of significant mean change in total symptom score (TSS) at 24 weeks with the experimental regimen was met (P = .003) with a mean reduction of 15.6 points which increased to 20.2 points at 48 weeks among those who rolled over to the phase 3 expansion study. In the control group, the mean TSS reduction was 9.2 points at 24 weeks. Additional findings showed that serum tryptase reduction of 50% or more was achieved by 53.9% of patient in the experimental arm experiencing compared with no patients in the control arm.

The agent also demonstrated a promising safety profile, with 96.5% of patients in the avapritinb arm completing treatment at 24 weeks vs 93.0% in the control arm. A total of 0.7% of patients in the avapritinb cohort compared with no patients in the control cohort discontinued treatment due to treatment-related adverse effects.

“Ayvakit has the potential to be the first approved medicine for non-advanced [systemic mastocytosis], 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,” Becker Hewes, MD, chief medical officer at Blueprint Medicines, concluded.


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. August 17, 2022. Accessed August 17, 2022. https://bit.ly/3Atb9lk

Related Videos
In the October edition of Snap Recap, we review the latest FDA news and the vote from the last ODAC meeting.
In this September edition of Snap Recap, we share our highlights from Prostate Cancer Awareness Month, news in the breast cancer space, and the latest FDA updates.
Implementing tax benefits for manufacturers who produce chemotherapy drugs may be one solution to increase drug production in the United States, according to Lucio N. Gordan, MD.
Lucio N. Gordan, MD, describes how his practice deals with increasing costs of limited chemotherapy agents to ensure that patients with cancer continue to receive treatment.
Lucio N. Gordan, MD, also discusses how increasing domestic manufacturing of chemotherapy may help in alleviating the ongoing shortages of carboplatin and cisplatin in the United States.
Kirollos Hanna, PharmD, BCPS, BCOP, FACCC, believes that national legislation can help to resolve the United States’ current dearth of cisplatin, as well as prevent future problems.
Using an AUC of 5 instead of an AUC of 6 can help to conserve cisplatin among patients with cancer, Kirollos Hanna, PharmD, BCPS, BCOP, FACCC says.
While there is a cisplatin shortage in the United States, the FDA has approved the importation of select chemotherapy drugs from China to help mitigate the scarcity of the agents.
Recommendations penned by the American Society of Clinical Oncology and Society for Gynecologic Oncology may be critical in managing the ongoing chemotherapy shortage, according to Michael Ganio, PharmD, MS, BCPS, FASHP.
Related Content