On 16 June 2021, the US Food and Drug Administration (FDA) approved avapritinib (Ayvakit™, Blueprint Medicines Corp.) for adult patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated haematological neoplasm (SM-AHN), and mast cell leukaemia (MCL).
Efficacy was evaluated in EXPLORER (NCT02561988) and PATHFINDER (NCT03580655), two multi-centre, single-arm, open-label clinical studies enrolling patients with AdvSM. The main efficacy outcome measure was overall response rate (ORR) per modified IWG-MRT-ECNM criteria, as adjudicated by a central committee. Additional efficacy measures were duration of response (DoR), time to response, and changes in individual measures of mast cell burden. Fifty-three patients received daily doses of avapritinib, up to 200 mg.
The ORR in all evaluable patients in both studies combined was 57% (95% confidence interval [CI] 42, 70) (n=53), with 28% complete remissions and 28% partial remissions. The median DoR was 38.3 months (95% CI 19, not estimable) and the median time to response was 2.1 months.
The most common adverse reactions (incidence ≥20%) in patients with AdvSM were oedema, diarrhoea, nausea, and fatigue/asthenia.
Avapritinib is not recommended for the treatment of patients with AdvSM with platelet counts of less than 50 x 109/L.
The recommended avapritinib dose is 200 mg orally once daily for patients with AdvSM.
Full prescribing information for Avvakit is available here.
This application was granted priority review, breakthrough designation and orphan drug designation.
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