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Indolent ISMAdvanced SMPDGFRA GIST
  Impact of ISM   
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  About AYVAKIT  
  Efficacy   
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Indolent ISMAdvanced SMPDGFRA GIST

STUDY DESIGN

PIONEER was designed to measure symptom relief and change in mast cell burden1,2

PIONEER: A phase 2, multipart, randomized, placebo-controlled, double-blind trial (N=212) evaluating the efficacy and safety of AYVAKIT 25 mg vs placebo at 24 weeks, both arms receiving concomitant BSC1,2

Key eligibility criteria: ≥18 years of age; centrally confirmed ISM diagnosis per WHO criteria; uncontrolled moderate to severe ISM symptoms (defined as ISM-SAF TSS ≥28) despite ≥2 BSC2

PIONEER study design

Best supportive care (BSC) is usually referred to as
symptom-directed therapies in clinical settings

SYMPTOM MEASUREMENT

  • Primary endpoint: Absolute mean change in ISM-SAF TSS compared with placebo + BSC from baseline to Week 241
  • Exploratory endpoints: Mean change in ISM-SAF individual symptom scores; mean change in most severe symptom score at Week 242

MAST CELL BURDEN MEASUREMENT

  • Select key secondary endpoints compared with placebo + BSC at Week 241,2:
      • Proportion of patients achieving:
    • ≥50% reduction in serum tryptase levels
    • ≥50% reduction in KIT D816V VAF or undetectable‡
    • ≥50% reduction in bone marrow mast cells or no aggregates
ISM-SAF TSS

ISM-SAF TSS

The ISM-SAF is a validated patient-reported outcome measure assessing 11 ISM signs and symptoms (abdominal pain, nausea, diarrhea, spots, itching, flushing, bone pain, fatigue, dizziness, headache, and brain fog)1,3§

*Data cutoff was June 23, 2022.2

†Patients had the option to enter part 3 of PIONEER, an open-label extension evaluating the long-term efficacy and safety of AYVAKIT 25 mg + BSC for up to 5 years. All eligible patients either
continued AYVAKIT 25 mg + BSC daily or switched from placebo + BSC to AYVAKIT 25 mg + BSC.1

‡In peripheral blood.1

§Symptom severity scores (scored 0 [no symptoms] to 10 [worst imaginable symptoms] daily) are combined to calculate the TSS from 0-110, with higher scores representing greater symptom
severity. A biweekly average in ISM-SAF TSS was used to evaluate efficacy endpoints.3

BSC=best supportive care; ISM=indolent systemic mastocytosis; ISM-SAF=Indolent Systemic Mastocytosis-Symptom Assessment Form; KIT=KIT proto-oncogene, receptor tyrosine kinase;
QD=every day; TSS=total symptom score; VAF=variant allele fraction; WHO=World Health Organization.

PIONEER reflects a heterogenous population of patients living with ISM2

Select baseline demographics and patient characteristics (AYVAKIT + BSC, n=141; placebo + BSC, n=71)1,2

AGE RANGE

Median age, years (range)

AYVAKIT + BSC: 50 (18-77)

Placebo + BSC: 54 (26-79)

SEX

AYVAKIT + BSC:

71% female, 29% male

Placebo + BSC:

76% female, 24% male

VARIED TRYPTASE LEVELS

Median serum tryptase,

ng/mL (range)

AYVAKIT + BSC: 38.4 (3.6-256)

Placebo + BSC: 43.7 (5.7-501.6)

POLYPHARMACY BURDEN

Median No. of BSC (range)

AYVAKIT + BSC: 3 (0-11)

Placebo + BSC: 4 (1-8)

MAST CELL BURDEN

Mast cell aggregates present

AYVAKIT + BSC: 75%

Placebo + BSC: 80%

VARIED SYMPTOM SEVERITY

Mean ISM-SAF TSS at

baseline (SD)

AYVAKIT + BSC: 50.2 (19.1)

Placebo + BSC: 52.4 (19.8)

93% of patients in the AYVAKIT + BSC arm were KIT positive, with 7% KIT undetectable1

Patients were optimized on a range of BSC2

  • Anti-immunoglobulin E antibody (omalizumab)
  • Glucocorticoids
  • Cromolyn sodium
  • H1 antihistamines
  • H2 antihistamines
  • Leukotriene inhibitors
  • Proton pump inhibitors

See how AYVAKIT reduced symptom and mast cell burden

EFFICACY

Patient portrayal

Female indolent systemic mastocytosis patient portrayal profile and child

References: 1. AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; November 2024. 2. Gotlib J et al. NEJM Evidence. 2023;2(6). Published online May 23, 2023. doi:10.1056/EVIDoa2200339 3. Padilla B et al. Orphanet J Rare Dis. 2021;16(1):434.

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INDICATION

AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM).

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

IMPORTANT SAFETY INFORMATION
INDICATION & IMPORTANT SAFETY INFORMATION

Cognitive Effects—Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 7.8% of patients with ISM who received AYVAKIT + best supportive care (BSC) versus 7.0% of patients who received placebo + BSC; <1% were Grade 3. Depending on the severity, withhold AYVAKIT and then resume at the same dose, or permanently discontinue AYVAKIT.

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. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks following the final dose.

Adverse Reactions—The most common adverse reactions (≥10%) in patients with ISM were eye edema, dizziness, peripheral edema, and flushing.

Drug Interactions—Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors or 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 visit www.fda.gov/medwatch.

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

References:

  1. AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; November 2024.
  2. Kristensen T et al. Am J Hematol. 2014;89(5):493-498.
  3. Garcia-Montero AC et al. Blood. 2006;108(7):2366-2372.
  4. Ungerstedt J et al. Cancers. 2022;14(16):3942.
  5. Pardanani A. Am J Hematol. 2023;98(7):1097-1116.
  6. Data on file. Blueprint Medicines Corporation, Cambridge, MA. 2023.
  7. Gülen T et al. J Intern Med. 2016;279(3):211-228.
  8. Theoharides TC et al. N Engl J Med. 2015;373(2):163-172.
  9. Gotlib J et al. NEJM Evidence. 2023;2(6). Published online May 23, 2023. doi:10.1056/EVIDoa2200339
  10. Gilreath JA et al. Clin Pharmacol. 2019;11:77-92.
  11. Evans EK et al. Sci Transl Med. 2017;9(414):eaao1690.
  12. Padilla B et al. Orphanet J Rare Dis. 2021;16(1):434.
  13. van Anrooij B et al. Allergy. 2016;71(11):1585-1593.
  14. WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2024 [cited April 24, 2024]. (WHO Classification of Tumours Series, 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chapters/63
  15. Dranitsaris G et al. J Oncol Pharm Pract. Published online December 27, 2023. doi:10.1177/10781552231221149
  16. Siebenhaar F et al. Immunol Allergy Clin North Am. 2014;34(2):433-447.
  17. Jennings SV et al. Immunol Allergy Clin North Am. 2018;38(3):505-525.
  18. Akin C, ed. Mastocytosis: A Comprehensive Guide. Springer; 2020.