Positive top-line results from PIONEER trial of Ayvakit in patients with non-advanced systemic mastocytosis achieved primary and all key secondary endpoints

Based on these topline data, Blueprint Medicines plans to submit a supplemental new drug application (sNDA) to the FDA for Ayvakit in-advanced SM in the fourth quarter of 2022, with a subsequent submission of a type II variation marketing authorization application to the European Medicines Agency (EMA) anticipated in 2023. In addition, Blueprint Medicines plans to present detailed data from the PIONEER trial at an upcoming medical meeting.

The trial, which was designed to assess Ayvakit plus best available care versus placebo plus best available care (control arm), achieved its primary endpoint with a highly significant difference in the mean change in total symptom score (TSS) at 24 weeks (p=0.003). TSS was assessed by the Indolent SM Symptom Assessment Form (ISM-SAF). The Ayvakit arm had a reduction of 15.6 points in mean TSS at 24 weeks, which continued to deepen to 20.2 points at 48 weeks in patients who rolled over to the Part 3 open-label extension study. At 24 weeks, the control arm had a reduction of 9.2 points in mean TSS.

In addition, the PIONEER trial met all key secondary endpoints, including significant improvements across all measures of mast cell burden. More than half of Ayvakit-treated patients had a greater than 50 percent reduction of serum tryptase, compared to no patients in the control arm (53.9% vs. 0%; p<0.0001). ayvakit was well-tolerated and had a favorable safety profile, and 96.5 percent of ayvakit-treated patients completed 24 weeks of therapy, compared to 93.0 percent for the control arm. overall, 0.7 percent of patients in the ayvakit arm and no patients in the control arm discontinued due to treatment-related adverse events.></0.0001).>

“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,” said Mariana Castells, M.D., Ph.D., Director, Mastocytosis Center, Brigham and Women’s Hospital, and an investigator on the PIONEER trial. “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.”

Top-line Data from the PIONEER Trial Part 2 of the registrational PIONEER trial was designed to evaluate the efficacy and safety of Ayvakit (25 mg once-daily dosing; N=141) versus control (N=71) over 24 weeks of treatment. Eligibility criteria include an indolent SM diagnosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of best available care. Patients were able to continue symptom-directed therapies while receiving Ayvakit or placebo. Results were reported as of a data cutoff date of June 23, 2022. Baseline data, including mean TSS, were consistent with Part 1 of the trial. The PIONEER study achieved its primary endpoint and all key secondary endpoints with Ayvakit showing highly significant improvements in patient-reported symptoms and objective measures of disease burden.

Ayvakit had a favorable safety profile compared to the control arm. The rate of adverse events (AEs) was 90.8 percent in the Ayvakit arm and 93.0 percent in the control arm. Serious AEs occurred in 5.0 percent of Ayvakit-treated patients, compared to 11.3 percent of patients in the control arm. Discontinuations due to treatment-related AEs occurred in 0.7 percent of Ayvakit-treated patients and 0 percent of patients in the placebo arm. The Ayvakit arm had a lower rate of cognitive AEs than the control arm (2.8% Ayvakit vs. 4.2% control), and there were no intracranial bleeding events. Treatment-related AEs reported in at least three patients in either arm and at least 5 percent of Ayvakit-treated patients included headache (7.8% Ayvakit vs. 9.9% control), nausea (6.4% Ayvakit vs 8.5% control), peripheral edema (6.4% Ayvakit vs. 1.4% control) and periorbital edema (6.4% Ayvakit vs. 2.8% control). In the Ayvakit arm, 93.0 percent of edema AEs were Grade 1 and the remainder were Grade 2.