Blueprint Medicines Corp (BPMC) has announced its 2025 corporate outlook, highlighting strategic initiatives aimed at leveraging its R&D capabilities for sustained growth. The announcement, made on January 12, 2025, includes positive Phase 1 trial results for BLU-808 and updated revenue projections for AYVAKIT (avapritinib). Blueprint Medicines projects a $4 billion peak revenue opportunity for its systemic mastocytosis (SM) franchise and expects to achieve $2 billion in AYVAKIT revenue by 2030.
BLU-808 Phase 1 Trial Results
BLU-808, a highly potent and selective oral wild type KIT inhibitor, demonstrated a wide therapeutic window in a Phase 1 trial involving healthy volunteers. The trial included single-ascending dose (SAD; n=56) and multiple-ascending dose (MAD; n=31, 14-day dosing) cohorts.
Safety: BLU-808 was well-tolerated at all doses tested. All treatment-emergent adverse events (AEs) in the MAD cohorts [1-12 mg once daily (QD)] in those who received BLU-808 were Grade 1. There were no serious AEs, no discontinuations or dose modifications due to AEs, and no significant changes in laboratory measures.
Pharmacokinetics: BLU-808 showed a half-life of approximately 40 hours, enabling once-daily dosing, and consistent, dose-dependent increases in drug exposure. In the MAD cohorts, all BLU-808 doses led to sustained target coverage, with mean plasma concentrations exceeding predicted KIT IC50 levels at ≥1 mg QD and IC90 levels at ≥3 mg QD.
Pharmacodynamics: BLU-808 showed dose-dependent serum tryptase responses, reflecting evidence of mast cell target engagement across multiple dose levels. In the SAD cohorts, reductions in tryptase were observed after a single dose of BLU-808. In the MAD cohorts, rapid, robust, and sustained reductions in tryptase were observed, with reductions below the lower limit of quantification (LLOQ) at multiple dose levels.
Percy Carter, Ph.D., Chief Scientific Officer at Blueprint Medicines, stated, "These Phase 1 data support the best-in-class potential of BLU-808, which was designed to achieve unique potency and selectivity enabling a tunable treatment approach and optimization of benefit-risk across a diverse set of mast cell-driven diseases." Based on these data, Blueprint Medicines plans to initiate proof-of-concept studies in chronic urticaria, allergic asthma, allergic rhinitis, allergic conjunctivitis, and mast cell activation syndrome.
Systemic Mastocytosis Franchise Expansion
Based on the strength of the global AYVAKIT launch, sustained growth in diagnosed SM patients, and new epidemiology data, Blueprint Medicines now estimates the peak revenue opportunity for its SM franchise is $4 billion, with $2 billion in annual revenues expected from AYVAKIT by 2030. The company previously provided guidance in October 2024 for AYVAKIT product revenue of $475 to $480 million for full-year 2024, representing an increase of more than 130 percent over 2023.
Additional Pipeline Updates
Blueprint Medicines has initiated the registration-enabling Phase 3 HARBOR trial of elenestinib, a next-generation KIT D816V inhibitor, in patients with indolent systemic mastocytosis (ISM). Additionally, the company is advancing CDK2 and CDK4 targeted protein degraders for breast cancer and other solid tumors.
Blueprint Medicines is completing the Phase 1 dose escalation study of its CDK2 inhibitor BLU-222 and plans to de-prioritize further investment in this program, while engaging strategic partners to advance its franchise of CDK programs.
2025 Corporate Goals
Key goals for 2025 include:
- Growing franchise leadership in SM.
- Delivering continued strong AYVAKIT revenue growth.
- Presenting additional long-term data from the PIONEER trial of AYVAKIT in ISM.
- Achieving reimbursement of AYVAKYT in ≥20 countries by the end of 2025.
- Activating sites and driving patient enrollment in the Phase 3 HARBOR trial of elenestinib in ISM.
- Achieving BLU-808 clinical proof-of-concept in allergic and inflammatory diseases.
- Nominating two development candidates, including the company's first targeted protein degrader, in the second half of 2025.
