Expert: Kinase inhibitor with dual JAK2 and IRAK1 inhibitory activity. Selective JAK2 inhibition (minimal JAK1 activity) reduces myeloproliferative signaling while sparing JAK1-mediated hematopoiesis, preserving platelet production. IRAK1 inhibition reduces NF-kB-driven inflammatory cytokine production that drives cytopenia. This dual mechanism uniquely enables use in severely thrombocytopenic MF patients (platelets <50x10^9/L) where ruxolitinib/fedratinib are contraindicated.

Everyday: Blocks two specific enzymes (JAK2 and IRAK1) that drive the abnormal growth of bone marrow cells in myelofibrosis. Most JAK inhibitors (like Jakafi) mainly hit JAK1/JAK2, but pacritinib uniquely hits IRAK1 — which matters because IRAK1 drives the inflammatory signaling that destroys platelets. This is why pacritinib works in patients with very low platelet counts where other JAK drugs are too risky.

Targets: []

Primary EP: [{"id":"per2-svr","name":"Spleen volume reduction >=35% at Week 24","type":"CO-PRIMARY","unit":"%","p_value":"0.001","results":[{"n":"16/74 evaluable","arm":"per2-200bid","label":"22% (200mg BID)","va

Safety: Diarrhea 48% all-grade (4% Gr3). Nausea 32%. Grade 3/4 bleeding 14% (vs 7% BAT). Grade >=3 cardiac events 9% (vs 19% BAT - actually lower). Mortality: 4.7% (200mg BID), 10.6% (400mg QD), 12.2% (BAT).

Primary EP: [{"id":"pac-ep1","name":"SVR >=35% at Week 24","type":"PRIMARY","results":[],"timepoint":"Week 24","description":"Confirmatory trial required by FDA post-accelerated approval. Must demonstrate spleen

Vonjo - MF (severe thrombocytopenia) - Ph3 - Confirmatory (PACIFICA) 2026-2027

JAK2/IRAK1 inhibitor for myelofibrosis with severe thrombocytopenia (platelets <50k). Accelerated FDA approval Feb 2022. KEY RISK: Accelerated approval requires PACIFICA confirmatory Phase 3 data. If PACIFICA fails, FDA could withdraw approval. Differentiator: ONLY JAK inhibitor approved for severely thrombocytopenic MF patients (Jakafi, Inrebic, Ojjaara all have platelet restrictions). IRAK1 inhibition is the mechanistic reason — it spares platelet production while still hitting the JAK2 myeloproliferative signal.