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). <\/p>\n
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.<\/p>\n
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.<\/p>\n
The most common adverse reactions (incidence \u226520%) in patients with AdvSM were oedema, diarrhoea, nausea, and fatigue\/asthenia.<\/p>\n
Avapritinib is not recommended for the treatment of patients with AdvSM with platelet counts of less than 50 x 109<\/sup>\/L.<\/p>\n The recommended avapritinib dose is 200 mg orally once daily for patients with AdvSM.<\/p>\n Full prescribing information for Avvakit is available here<\/a>.<\/p>\n This application was granted priority review, breakthrough designation and orphan drug designation.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n