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Advanced systemic mastocytosis (AdvSM)

Get to know AYVAKIT for your AdvSM population

A targeted treatment for adults with AdvSM

Designed for potent and selective inhibition of KIT D816V1

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AdvSM overview

10%-20%

of the total systemic mastocytosis (SM) population is AdvSM, a rare, clonal, mast cell neoplasm2-4

~95%

of AdvSM cases are primarily driven by the KIT D816V mutation5-9

Organ damage and shortened survival

are 2 impacts of AdvSM. Symptoms can be debilitating, severe, and unpredictable4,6,7,10-12

Subtypes of AdvSM8,12:

Aggressive systemic mastocytosis (ASM)

Associated hematological neoplasm (SM-AHN)

Mast cell leukemia (MCL)

AdvSM is associated with shortened overall survival (OS)7,10

Median OS for patients with AdvSM4,10

Bar graph showing bar one as ASM (n=41) at 3.5 years, bar two as SM-AHN (n=138) at 2 years, and bar three as MCL (n=4) at less than 6 months

OS was examined in a retrospective study at the Mayo Clinic between 1976 and 2007. Median follow-up was 20.7 months. A later study with 23 MCL patients demonstrated a median OS for patients with MCL of 1.9 years, with a 10-year survival of 29.9%.4,10

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AYVAKIT for AdvSM

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Efficacy across
AdvSM subtypes1

AYVAKIT demonstrated efficacy across advanced SM subtypes (N=53) with a 57% overall response rate (ORR) (95% CI: 42%, 70%)*

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Demonstrated complete
remission (CR)1

CR with full or partial hematologic recovery (CRh) was seen in 28% of 53 evaluable AdvSM patients

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Generally well tolerated in clinical studies1

In 2 separate clinical trials, the majority of adverse events (AEs) were Grade 1 or 2 for patients with AdvSM subtypes

The most common adverse reactions (≥20%) at all doses were edema, diarrhea, nausea, and fatigue/asthenia. For those treated with the recommended starting dose, serious adverse reactions were seen in 34% of patients and fatal adverse reactions occurred in 2.5% of patients. No specific adverse reaction leading to death was reported in more than 1 patient

*Median duration of follow-up was 11.6 months (95% CI: 9.9 to 16.3 months).1

Efficacy and safety of AYVAKIT were evaluated in EXPLORER and PATHFINDER, multicenter, single-arm, open-label clinical trials for patients with advanced SM. Adult patients (N=53; median age 67) were evaluable for a response across the 2 trials. EXPLORER: Phase 1 dose-finding study to determine maximum tolerated dose where patients received a starting, once-daily dose of 30 mg-400 mg. PATHFINDER: Phase 2 study evaluating efficacy and safety where patients received a starting, once-daily dose of 200 mg. Efficacy was based on ORR in patients with advanced SM dosed at up to 200 mg daily, per modified IWG-MRT-ECNM criteria as adjudicated by the central committee and defined as patients who achieved a complete remission, complete remission with full or partial hematologic recovery, or partial remission. In the subgroup of patients with MCL, the efficacy was based on CR.1,13,14

Want to know more? Contact a National Account Executive for more information about AYVAKIT for AdvSM.
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Learn more about the value of AYVAKIT for AdvSM

EXPLORER and PATHFINDER clinical trial overviews
See AYVAKIT efficacy in clinical studies
VIEW EFFICACY RESULTSGo to external site
EXPLORER and PATHFINDER clinical trial safety data
Explore the safety of AYVAKIT for AdvSM
VIEW AYVAKIT SAFETYGo to external site
AYVAKIT AdvSM leave behind
Download this resource for AdvSM disease burden and AYVAKIT information at a glance
DOWNLOAD AdvSM LEAVE BEHINDDownload resource
Presentations and publications from Blueprint Medicines
Access scientific presentation and publication highlights about AYVAKIT for AdvSM

IWG-MRT-ECNM=International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM).

INDICATION

AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with advanced SM (AdvSM) including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).

Limitations of Use: AYVAKIT is not recommended for the treatment of patients with AdvSM with platelet counts of <50 x 109/L.

INDICATION & IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION

Intracranial Hemorrhage — Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (e.g., subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT in clinical trials. In AdvSM patients who received AYVAKIT at 200 mg daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts ≥50 x 109/L prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts.

Monitor patients closely for risk factors of ICH which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia. Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH. Permanently discontinue AYVAKIT if ICH of any grade occurs.

A platelet count must be performed prior to initiating therapy. AYVAKIT is not recommended in AdvSM patients with platelet counts <50 x 109/L. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of <50 x 109/L by treatment interruption or dose reduction.

Cognitive Effects — Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 33% of 995 patients overall in patients who received AYVAKIT in clinical trials including 28% of 148 AdvSM patients (3% were Grade ≥3). Depending on the severity and indication, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.

Photosensitivity — AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients. Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment.

Embryo-Fetal Toxicity — AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks following the final dose.

Adverse Reactions — The most common adverse reactions (≥20%) were edema, diarrhea, nausea, and fatigue/asthenia.

Drug Interactions — Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong or moderate CYP3A inducers. If contraception requires estrogen, limit ethinyl estradiol to ≤20 mcg unless a higher dose is necessary.

To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA‑1088 or www.fda.gov/medwatch.

AYVAKIT is available in 25-mg, 50-mg, 100-mg and 200-mg tablets.

Please click here to see the full Prescribing Information for AYVAKIT.

References:

  1. AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; May 2023.
  2. Ungerstedt J, Ljung C, Klimkowska M, et al. Clinical outcomes of adults with systemic mastocytosis: a 15-year multidisciplinary experience. Cancers (Basel). 2022 Aug 16;14(16):3942.
  3. Cohen SS, Skovbo S, Vestergaard H, et al. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol. 2014 Aug;166(4):521-8.
  4. Sperr WR, Kundi M, Alvarez-Twose I, et al. International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study. Lancet Haematol. 2019;6(12):e638-e649.
  5. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373(2):163-172.
  6. Jennings SV, Slee VM, Zack RM, et al. Patient perceptions in mast cell disorders. Immunol Allergy Clin North Am. 2018;38(3):505-525.
  7. Verstovsek S. Advanced systemic mastocytosis: the impact of KIT mutations in diagnosis, treatment, and progression. Eur J Haematol. 2013;90(2):89-98.
  8. Gilreath JA, Tchertanov L, Deininger MW. Novel approaches to treating advanced systemic mastocytosis. Clin Pharmacol. 2019;11:77-92.
  9. Garcia-Montero AC, Jara-Acevedo M, Teodosio C, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108(7):2366-2372.
  10. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113(23):5727-5736.
  11. Gülen T, Ljung C, Nilsson G, Akin C. Risk factor analysis of anaphylactic reactions in patients with systemic mastocytosis. J Allergy Clin Immunol Pract. 2017;5(5):1248-1255.
  12. Gotlib J, Pardanani A, Akin C, et al International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013;121(13):2393-2401.
  13. (PATHFINDER) study to evaluate efficacy and safety of avapritinib (BLU-285), a selective KIT mutation-targeted tyrosine kinase inhibitor, in patients with advanced systemic mastocytosis. ClinicalTrials.gov identifier: NCT03580655. Updated August 7, 2024. Accessed September 3, 2024. https://clinicaltrials.gov/study/NCT03580655
  14. (EXPLORER) study of BLU-285 in patients with advanced systemic mastocytosis (AdvSM) and relapsed or refractory myeloid malignancies. ClinicalTrials.gov identifier: NCT02561988. Updated March 17, 2023. Accessed September 3, 2024. https://clinicaltrials.gov/study/NCT02561988

INDICATION

AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with advanced SM (AdvSM) including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).

Limitations of Use: AYVAKIT is not recommended for the treatment of patients with AdvSM with platelet counts of <50 x 109/L.

INDICATION & IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION

Intracranial Hemorrhage — Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (e.g., subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT in clinical trials. In AdvSM patients who received AYVAKIT at 200 mg daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts ≥50 x 109/L prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts.

Monitor patients closely for risk factors of ICH which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia. Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH. Permanently discontinue AYVAKIT if ICH of any grade occurs.

A platelet count must be performed prior to initiating therapy. AYVAKIT is not recommended in AdvSM patients with platelet counts <50 x 109/L. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of <50 x 109/L by treatment interruption or dose reduction.

Cognitive Effects — Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 33% of 995 patients overall in patients who received AYVAKIT in clinical trials including 28% of 148 AdvSM patients (3% were Grade ≥3). Depending on the severity and indication, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.

Photosensitivity — AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients. Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment.

Embryo-Fetal Toxicity — AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks following the final dose.

Adverse Reactions — The most common adverse reactions (≥20%) were edema, diarrhea, nausea, and fatigue/asthenia.

Drug Interactions — Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong or moderate CYP3A inducers. If contraception requires estrogen, limit ethinyl estradiol to ≤20 mcg unless a higher dose is necessary.

To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA‑1088 or www.fda.gov/medwatch.

AYVAKIT is available in 25-mg, 50-mg, 100-mg and 200-mg tablets.

Please click here to see the full Prescribing Information for AYVAKIT.

References:

  1. AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; May 2023.
  2. Ungerstedt J, Ljung C, Klimkowska M, et al. Clinical outcomes of adults with systemic mastocytosis: a 15-year multidisciplinary experience. Cancers (Basel). 2022 Aug 16;14(16):3942.
  3. Cohen SS, Skovbo S, Vestergaard H, et al. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol. 2014 Aug;166(4):521-8.
  4. Sperr WR, Kundi M, Alvarez-Twose I, et al. International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study. Lancet Haematol. 2019;6(12):e638-e649.
  5. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373(2):163-172.
  6. Jennings SV, Slee VM, Zack RM, et al. Patient perceptions in mast cell disorders. Immunol Allergy Clin North Am. 2018;38(3):505-525.
  7. Verstovsek S. Advanced systemic mastocytosis: the impact of KIT mutations in diagnosis, treatment, and progression. Eur J Haematol. 2013;90(2):89-98.
  8. Gilreath JA, Tchertanov L, Deininger MW. Novel approaches to treating advanced systemic mastocytosis. Clin Pharmacol. 2019;11:77-92.
  9. Garcia-Montero AC, Jara-Acevedo M, Teodosio C, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108(7):2366-2372.
  10. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113(23):5727-5736.
  11. Gülen T, Ljung C, Nilsson G, Akin C. Risk factor analysis of anaphylactic reactions in patients with systemic mastocytosis. J Allergy Clin Immunol Pract. 2017;5(5):1248-1255.
  12. Gotlib J, Pardanani A, Akin C, et al International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013;121(13):2393-2401.
  13. (PATHFINDER) study to evaluate efficacy and safety of avapritinib (BLU-285), a selective KIT mutation-targeted tyrosine kinase inhibitor, in patients with advanced systemic mastocytosis. ClinicalTrials.gov identifier: NCT03580655. Updated August 7, 2024. Accessed September 3, 2024. https://clinicaltrials.gov/study/NCT03580655
  14. (EXPLORER) study of BLU-285 in patients with advanced systemic mastocytosis (AdvSM) and relapsed or refractory myeloid malignancies. ClinicalTrials.gov identifier: NCT02561988. Updated March 17, 2023. Accessed September 3, 2024. https://clinicaltrials.gov/study/NCT02561988

The information on this website is intended solely for use by US payers, formulary committees, or other similar entities. These materials are not intended to be used by healthcare practitioners for the purpose of making individual patient prescribing or treatment decisions.

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