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.