FDA Approves Avapritinib for Advanced Systemic Mastocytosis

FDA

The FDA has approved avapritinib (Ayvakit) for the treatment of adult patients with advanced systemic mastocytosis, including those with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.¹

The regulatory decision was supported by data from the phase 1 EXPLORER (NCT02561988) and phase 2 PATHFINDER (NCT03580655) trials, which showed that the agent elicited an objective response rate of 57% (95% CI, 42%-70%) in all 53 evaluable patients in both trials combined at median follow-up of 11.6 months. Notably, 28% of patients achieved complete remissions (CRs) with the agent and 28% experienced partial remissions (PRs).

Moreover, the median duration of response with avapritinib was 38.3 months (95% CI, 19–not estimable) and the median time to response was 2.1 months.

"Advanced systemic mastocytosis is a debilitating disease characterized by extensive damage in multiple organ systems due to mast cell infiltration, and new treatment options are urgently needed to address these life-threatening complications," Daniel DeAngelo, MD, PhD, chief of the Division of Leukemia at Dana-Farber Cancer Institute, stated in a press release.² "Avapritinib will clearly establish a new standard of care for patients with advanced systemic mastocytosis. The FDA approval was based on data showing robust and durable responses, including complete remissions, and a favorable safety profile. For [patients with] advanced systemic mastocytosis, the approval of avapritinib shifts the treatment paradigm toward precision therapy that targets the primary driver of mastocytosis."

For the trials, response to treatment was examined using modified IWG-MRT-ECNM criteria, and assessments were based on at least 12 weeks of response duration, resolution of at least 1 finding of non-hematologic and hematologic organ damage, and 50% or higher reductions in biomarker response, mast cell burden, and serum tryptase. Moreover, the ORR in the US prescribing information is defined as CR with full or partial hematologic recovery, or PR.

The recommended daily dose of avapritinib in patients with advanced systemic mastocytosis is 200 mg. The agent is available in 200 mg, 100 mg, 50 mg and 25 mg dose strengths for this patient population.

Regarding safety, the toxicities most frequently experienced with the agent, that were reported in at least 20% of participants, included edema, diarrhea, nausea, and fatigue/asthenia.

Warnings and precautions regarding the agent include intracranial hemorrhage, cognitive effects and embryo-fetal toxicity. Avapritinib is not recommended for use in patients with advanced systemic mastocytosis who have low platelet counts, defined as less than 50,000/µL, which is consistent with current eligibility criteria in EXPLORER and PATHFINDER.

"People with advanced systemic mastocytosis face a scary, uncertain future due to life-threatening complications of the disease, as well as debilitating symptoms that often profoundly alter their ability to perform daily activities, and the FDA approval of a new therapy, [avapritinib], brings much needed hope to these patients," Valerie Slee, Board Chair of The Mast Cell Disease Society, added in the press release.

References

1. FDA approves avapritinib for advanced systemic mastocytosis. News release. FDA. June 16, 2021. Accessed June 16, 2021. https://bit.ly/3xuLxQC
2. FDA approves Blueprint Medicines' AYVAKIT (avapritinib) for the treatment of adults with advanced systemic mastocytosis. News release. Blueprint Medicines Corporation. June 16, 2021. Accessed June 16, 2021. https://yhoo.it/3xFzHDJ