The FDA has approved avapritinib for adult patients with indolent systemic mastocytosis based on findings from the phase 2 PIONEER trial.
The FDA has approved avapritinib (Ayvakit) as a treatment option for adult patients with indolent systemic mastocytosis.1
This approval is supported by findings from the phase 2 PIONEER trial (NCT03731260), in which avapritinib added to to best supportive care (BSC) significantly improved outcomes vs BSC alone in this population.
Avapritinib also demonstrated to have favorable tolerability and most toxicities were mild to moderate in severity.
"[Avapritinib] is the first and only medicine approved by the FDA to treat indolent systemic mastocytosis, marking a shift in the treatment paradigm from supportive care to disease modifying therapy," said Becker Hewes, MD, chief medical officer at Blueprint Medicines, in a press release. "In addition, [avapritinib] is the only treatment approved across the spectrum of indolent and advanced systemic mastocytosis. 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."
In the double-blind, placebo-controlled, phase 2 PIONEER study, patients were given avapritinib at 25 mg daily plus BSC or placebo plus BSC. A total of 141 patients were enrolled to receive avapritinib vs 71 to receive placebo.
The primary end point in the study was mean change in total symptom score (TSS), and the secondary end points included 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.
Findings showed that treatment with avapritinib met its primary end point of significant difference of mean change in TSS at 24 weeks vs placebo (P = .003). Patients given avapritinib had a reduction of 15.6 points in mean TSS at week 24 and the TSS continued to decrease to 20.2 points at week 48 in patients who rolled over to the part 3 open-label extension study. In the control arm, there was only a 9.2-point in mean TSS at week 24. In the avapritinib arm, patients had a significantly higher rate of at least 50% reduction of serum tryptase vs no patients in the control arm: 53.9% vs 0%, respectively (P < .0001).
For safety, treatment with avapritinib was well tolerated, and the agent had a favorable safety profile overall. Treatment was completed by 96% of patients in the avapritinib arm vs 93% in the placebo arm. Adverse events (AEs) were reported in 90.8% of the avapritinib arm vs 93% of the control arm, and serious AEs occurred in 5% vs 11.3%, respectively.
Treatment-related AEs (TRAEs) observed in the study included 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 TRAEs led to treatment discontinuations, and 0.7% of patients discontinued treatment in the avapritinib arm vs 0% patients in the control arm.
"After decades of caring for people with indolent systemic mastocytosis, I have seen firsthand its profound impact on patients' underlying mast cell burden, symptoms, physical and mental health, and ability to work and participate in daily activities," said Cem Akin, MD, PhD, professor of medicine at the University of Michigan, and an investigator on the PIONEER trial, in the press release. "Despite the use of multiple supportive care treatments, a considerable number of patients with indolent systemic mastocytosis continue to experience a substantial disease burden. [Avapritinib] advances the treatment of indolent systemic mastocytosis by targeting KIT D816V, the primary underlying cause of the disease, and establishes a new standard of care for a broad population of patients with this disorder. [Avapritinib] delivered statistically significant and consistent clinical improvements in the PIONEER trial, and based on these practice-changing data, I feel a tremendous sense of hope for the future for all those affected by the disease."