Vonjo (pacritinib) / SOBI - LARVOL DELTA

Computational Repurposing of Janus Kinase Inhibitors as Potential Therapeutic Candidates for Alzheimer's Disease. (PubMed, Medicina (Kaunas)) - "Molecular docking indicated that pacritinib and momelotinib showed relatively favorable predicted interactions with the hub proteins, while NMA revealed differences in the predicted flexibility of the docked complexes. Collectively, these findings provide mechanistic insights into the potential effects of JAK inhibitors in AD and identify pacritinib as a computationally prioritized candidate that warrants experimental validation in appropriate AD models. However, as this study is based solely on computational analyses without wet-lab validation, the findings should be considered hypothesis-generating in silico evidence, and the potential safety concerns of pacritinib require further investigation."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Inflammation • BCL2 • STAT3

Comparative Efficacy of Drug Therapies on Spleen Size and Symptom Reduction in Myelofibrosis: A Frequentist Network Meta-Analysis (SOHO 2026) - "Single-agent JAKis demonstrated variable efficacy similar to or worse than that of ruxolitinib, with an OR of 0.88 (95%CI:0.58–1.34) for momelotinib, 0.52 (95% CI, 0.05–6.05) for fedratinib, 0.35 (95% CI, 0.04–3.20) for bezacitinib, 0.17 (95% CI, 0.02–1.41) for jaktinib, and 0.16 (95% CI, 0.02–1.52) for pacritinib...Compared with BAT, pacritinib showed an OR of 3.43 (95% CI, 0.39–29.76), navtemadlin 3.26 (95% CI, 0.92–11.53), and momelotinib 3.10 (95% CI, 1.13–8.53)... In JAKi-naïve myelofibrosis, combination strategies with navitoclax or pelabresib added to ruxolitinib demonstrated the greatest spleen responses. Ruxolitinib remains similar or superior to single-agent JAKis in spleen or symptom response. In ruxolitinib-exposed patients with myelofibrosis, fedratinib, momelotinib, and pacritinib showed clinically meaningful activity compared with BAT, and fedratinib was numerically better than others."

Retrospective data • Myelofibrosis • Oncology

Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. (PubMed, Blood Adv) - "Pacritinib inhibited ACVR1 with greater potency (IC50 = 16.7 nM; Cmax:IC50 = 12.7) than momelotinib (IC50 = 52.5 nM; Cmax:IC50 = 3.2), fedratinib (IC50 = 273 nM; Cmax:IC50 = 1.0), or ruxolitinib (IC50 >1000; Cmax:IC50 <0.01). Among patients on PERSIST-2 who were not TI at baseline based on Gale criteria, a significantly greater proportion became TI on pacritinib compared to best available therapy (37% vs. 7%, P=0.001), and significantly more had a ≥50% reduction in transfusion burden (49% vs. 9%, P<0.0001). These data indicate that the anemia benefit of the JAK2/IRAK1 inhibitor pacritinib may be a function of potent ACVR1 inhibition."

Journal • Anemia • Hematological Disorders • Myelofibrosis • ACVR1 • IRAK1

Sobi Receives US FDA Fast Track Designation for pacritinib in VEXAS Syndrome (GlobeNewswire) - "PAXIS (NCT06782373) is a Phase II, randomized, multicenter, double-blind, placebo-controlled, dose-finding trial followed by an open-label period, designed to evaluate the efficacy and safety of pacritinib in preventing disease flares in patients with VEXAS syndrome following glucocorticoid tapering....Topline data is expected in 2027."

Fast track • P2 data • Immunology • Inflammation

Real-World Use of Pacritinib in Myelofibrosis: Results From the TriNetX Analysis on Patient Characteristics, Treatment Patterns, and Outcomes in Patients With Platelets ≥50 × 109/L at Initiation (TRIPAC) (SOHO 2026) - "Among patients with prior JAK-inhibitor exposure, 95.8% (46 of 48) received ruxolitinib. In this real-world retrospective analysis of patients with MF and baseline PLT ≥50 × 109/L, treatment with pacritinib resulted in a notable proportion of patients who experienced increases in hematologic parameters at 6 months. These findings provide real-world evidence supporting pacritinib use in patients with MF and PLT ≥50 × 109/L at initiation. ACVR1: activin A receptor type 1 activity, IRAK1: interleukin-1 receptor-associated kinase 1, JAK1/2: Janus kinase 1/2, NR: not reached, OS: overall survival, PLT: platelet count."

Clinical • Real-world • Real-world evidence • Myelofibrosis • Oncology • ACVR1 • IRAK1 • JAK1

Pacritinib in transplant-eligible myelofibrosis: final analysis of the phase II HOVON-134 trial. (PubMed, Bone Marrow Transplant) - No abstract available

Journal • P2 data • Myelofibrosis • Transplantation

POSTPONE: Pacritinib in Participants With Metastatic Castrate-Resistant Prostate Cancer That Progressed on or After Prior Treatment With Androgen Receptor Signaling Inhibitors (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: Medical College of Wisconsin | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA). (ASCOBT 2024) - P1/2 | "Pacritinib at 200mg BID is safe and tolerable in pts with solid tumors. IRAK1 inhibition appears to modulate immune cell populations both in the tumor microenvironment and systemic circulation. Dose expansion is underway, with potential signal of disease control in HPB tumors."

Clinical • P1/2 data • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Immune Modulation • Immunology • Lung Cancer • Myelofibrosis • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • FLT3 • IRAK1 • JAK2 • PD-1

Risk-adjusted safety analysis of the oral JAK2/IRAK1 inhibitor pacritinib in patients with myelofibrosis. (PubMed, EJHaem) - "To account for longer treatment durations on the pacritinib arms compared to best available therapy (BAT), we present a risk-adjusted safety analysis of event rates accounting for different time on treatment. While the rate of overall events was higher on pacritinib compared to BAT, the rate of fatal events was lower, and there was no excess in bleeding, cardiac events, secondary malignancy, or thrombosis on pacritinib, including in patients with severe thrombocytopenia."

Journal • Cardiovascular • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • Thrombosis • IRAK1 • JAK2

Comparative Efficacy, Hematologic Safety, and Treatment Persistence of FDA-Approved Janus Kinase Inhibitors in Myelofibrosis: Integrating the 2026 Approval of Once-Daily Ruxolitinib XR—A Systematic Review and Bayesian Network Meta-Analysis (SOHO 2026) - "For spleen volume reduction ≥35% at Week 24, ruxolitinib immediate release (IR)/XR demonstrated the highest efficacy (OR, 44.2; 95% credible interval [CrI], 14.1–118.5; surface under the cumulative ranking curve [SUCRA] = 0.95), followed by fedratinib (OR, 32.1; 95% CrI, 9.1–90.3; SUCRA = 0.81), momelotinib (OR, 18.4; 95% CrI, 6.2–49.7; SUCRA = 0.63), and pacritinib (OR, 11.6; 95% CrI, 3.4–31.2; SUCRA = 0.49). Ruxolitinib XR maintained superior efficacy and treatment persistence, whereas momelotinib and pacritinib demonstrated phenotype-specific safety advantages, supporting a personalized therapeutic approach in myelofibrosis, with overall low risk of bias across included trials using RoB 2.0."

Retrospective data • Review • Myelofibrosis • Oncology

Real-World Treatment Patterns and Outcomes in Patients With Myelofibrosis Treated With First-Line Pacritinib or Ruxolitinib (SOHO 2026) - "These real-world data show that first-line pacritinib is used in advanced cytopenic myelofibrosis patients with lower platelet counts, whereas ruxolitinib is used in patients with higher platelet counts. Despite these differences and the poorer prognosis observed among cytopenic patients, pacritinib- and ruxolitinib-treated patients appeared to have similar 6-month survival probabilities, with both treatments achieving clinically meaningful improvement in spleen size and symptom burden. This abstract was accepted at EHA2026."

Clinical • HEOR • Real-world • Real-world evidence • Myelofibrosis • Oncology

Prospera (ABNL-MARRO 002): A randomized phase 2 study of pacritinib vs. hydroxyurea in patients with advanced proliferative chronic myelomonocytic leukemia (CMML) (ASH 2025) - P2 | "In the phase 3 DACOTA trial (Itzykson et al., JCO 2022),decitabine modestly delayed leukemic transformation compared to HU but did not improve event-free oroverall survival and was associated with increased early mortality. The primary endpoint is CBR at Week 24, defined by modified IWG MDS/MPNcriteria incorporating hematologic improvement, spleen volume reduction, and symptom response.Secondary endpoints include CBR at any time, duration of response, event-free survival, leukemia-freesurvival, and overall survival.Correlative studies will assess treatment-related changes in clonal dynamics, cytokine signaling, andhematopoietic composition using longitudinal peripheral blood and bone marrow sampling. Single-celltranscriptomic and immunophenotypic profiling will be employed to characterize pacritinib's impact onboth the malignant clone and the surrounding immune microenvironment."

Clinical • Metastases • P2 data • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • IRAK1

Selinexor Alone and in Combination With JAK Inhibitors Suppresses Pro-Inflammatory Cytokine Secretion From Primary Myelofibrosis Cells Ex Vivo (SOHO 2026) - P3 | " NF-κB transcriptional activity was assessed in TNFα-stimulated UKE1 (JAK2-V617F) and ELF-153 (JAK2wt) cells treated with selinexor (250 nM) ± JAKi (100 nM; ruxolitinib, momelotinib, pacritinib). XPO1 inhibition suppresses NF-κB-regulated cytokine production in myelofibrosis PBMCs, both alone and with JAKis. These findings support selinexor plus ruxolitinib as a potential disease-modifying strategy in JAKi-naïve myelofibrosis currently under evaluation in SENTRY. Previously presented at ASH 2025."

Combination therapy • IO biomarker • Preclinical • Myelofibrosis • Oncology • CALR • IL6 • JAK2 • TLR8 • XPO1

Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling. (PubMed, Front Immunol) - "We also discuss the non-canonical functions of IRAK1 in transcriptional regulation, antiviral defense, cytoskeletal organization, and oncogenic signaling, and evaluate current pharmacological inhibitors of IRAK1, including Pacritinib, JH-X-119-01, 1, 4-naphthoquinone, and rosoxacin. Overall, this review provides a systematic, data-informed framework for prioritizing phosphosite-specific functional studies to identify phospho-dependent interaction interfaces as potential targets for precision clinical interventions and biomarker development in inflammatory diseases and cancer."

IO biomarker • Journal • Review • Oncology • Targeted Protein Degradation • IL1R1 • IRAK1

Quantifying the Patient Experience: A Systematic Review of JAK Inhibitor Impact on Symptom Scores, Health-Related Quality of Life, and Sleep in Myelofibrosis (SOHO 2026) - "JAK inhibitors (ruxolitinib, fedratinib, pacritinib, and momelotinib) are approved for MF, yet a quantitative synthesis of their effects on symptom burden and sleep disturbance remains absent. JAK inhibitor therapy produces significant, clinically meaningful reductions in symptom burden, fatigue, night sweats, and HRQoL impairment in patients with MF. Sleep disturbance improvement is supported by indirect evidence from the EORTC QLQ-C30 insomnia subscale and night sweats resolution, although the absence of dedicated sleep instruments limits certainty (Grading of Recommendations, Assessment, Development, and Evaluation: very low for sleep domain). Future MF trials should incorporate validated sleep-specific measures such as the Pittsburgh Sleep Quality Index to directly address this evidence gap."

Clinical • HEOR • Review • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Adaptations in pacritinib usage for myelofibrosis and thrombocytopenia since FDA approval. (PubMed, Expert Rev Hematol) - No abstract available

FDA event • Journal • Hematological Disorders • Myelofibrosis • Thrombocytopenia

Mortality, Thrombotic, Hemorrhagic, and Cardiovascular Outcomes With JAK1/JAK2/IRAK1 Inhibitors Versus Conventional Cytoreductive Therapy in Myeloproliferative Neoplasms: A Real-World Propensity-Matched Analysis (SOHO 2026) - "Patients: Adults aged 18–75 years with MPN-spectrum diagnoses (polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic myeloproliferative disease, CML, MDS; ICD-10 codes D45, D46, D47.1, D47.3, D47.4, D47.Z9, C92.1) on/after January 1, 2010, initiating a JAK1/JAK2/IRAK1 inhibitor (ruxolitinib, fedratinib, pacritinib, momelotinib; n = 4251) or non-JAK cytoreductive agent (hydroxyurea, anagrelide, interferon alfa-2a/2b; n = 14448) within 3 months of diagnosis... JAK1/JAK2/IRAK1 inhibitor therapy was associated with markedly higher 3-year mortality, hospitalization, major bleeding, VTE, and heart failure compared with non-JAK cytoreductive therapy. Because JAK inhibitors are preferentially used in higher-risk MPN phenotypes imperfectly captured by ICD coding, residual confounding by unmeasured disease severity likely contributes. Prospective comparative effectiveness studies with granular severity adjustment are needed."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Essential Thrombocythemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • IRAK1 • JAK1 • JAK2

Consistency of pacritinib for spleen and symptom reduction in patients with myelofibrosis regardless of cytopenias. (ASCO 2023) - P3 | "Pacritinib demonstrates consistent efficacy for spleen and symptom response in patients with MF regardless of blood counts. This consistent effect may be related to pacritinib’s unique kinome profile and its ability to be delivered at full dose in patients regardless of cytopenias. Clinical trial information: NCT01773187, NCT02055781."

Clinical • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1

Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: University of Washington | Trial completion date: Nov 2026 ➔ Nov 2027 | Trial primary completion date: Nov 2026 ➔ Nov 2027

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytosis • Transplantation

Pacritinib Response Is Associated With Overall Survival in Myelofibrosis: PERSIST-2 Landmark Analysis of Survival. (PubMed, Eur J Haematol) - P3 | "In patients with myelofibrosis and platelets ≤ 100 × 109/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781."

Journal • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1 • JAK2

Real-World Hematologic and Spleen Outcomes With Pacritinib in Myelofibrosis-Associated Anemia: A Report of Two Cases (SOHO 2026) - " Case 1 was a 69-year-old man with JAK2 V617F–positive, Dynamic International Prognostic Scoring System (DIPSS) low-risk primary MF, a JAK2-only mutation profile, recent peripheral blasts <1%, anemia (hemoglobin [Hb] 120 g/L), platelets 120 × 109/L, white blood cells (WBCs) 6.07 × 109/L, constitutional symptoms, and ultrasound-assessed splenomegaly (28 cm) despite ruxolitinib therapy (15 mg twice daily). In these two early real-world cases, pacritinib was associated with improved or preserved Hb, stable leukocyte and platelet counts, and measurable spleen reduction in Case 1. These findings support further evaluation of pacritinib in MF-associated anemia and cytopenias."

Clinical • Real-world • Real-world evidence • Myelofibrosis • Oncology • ACVR1 • ASXL1 • IRAK1 • JAK1

Preliminary Data from the Phase I/II Study of TP-3654, a Selective Oral PIM1 Kinase Inhibitor, in Patients with Myelofibrosis Previously Treated with or Ineligible for JAK Inhibitor Therapy (ASH 2022) - P1/2 | "TP-3654 showed less hematopoietic inhibition than Janus kinase (JAK) inhibitors (ruxolitinib, pacritinib and momelotinib) in in vitro human megakaryocyte and erythrocyte cell colony formation. The preliminary clinical data in dose escalation show: 1) encouraging signs of clinical activity in spleen volume reduction, symptom improvement, and cytokine reduction with TP-3654 monotherapy in patients previously treated with JAK inhibitors, 2) TP-3654 is well tolerated with limited myelosuppressive adverse events. The non-clinical findings and preliminary clinical safety/efficacy data support accelerated development and assessment of TP-3654 as the optimal partner for combination with JAK inhibitors."

Clinical • P1/2 data • Hematological Disorders • Immunology • Myelofibrosis • CALR • IL18 • MMP9 • PIM1 • TIMP1

JAK Inhibitors vs Traditional Therapy for Myelofibrosis: A Meta-Analysis of Randomized Clinical Trials (SOHO 2026) - "The pharmacological standard of care is the Janus kinase (JAK) inhibitor class (eg, ruxolitinib, pacritinib, momelotinib, fedratinib), which targets key disease drivers. However, traditional therapies, often grouped as best available therapy (BAT), including hydroxyurea and hematopoietic cell transplant, remain a significant comparator...The limitations in the new trials should be kept in mind while interpreting the results. CI: confidence interval, OR: odds ratio, RR: relative risk."

Retrospective data • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Comparative Efficacy and Safety of Next-Generation JAK Inhibitors (Fedratinib, Pacritinib, and Momelotinib) in Myelofibrosis: A Systematic Review and Meta-Analysis (SOHO 2026) - "While ruxolitinib remains the first-approved JAK inhibitor, three next-generation agents—fedratinib, pacritinib, and momelotinib—have since received regulatory approval, each addressing distinct unmet needs. Next-generation JAK inhibitors demonstrate significant and consistent efficacy over comparators in myelofibrosis. Fedratinib leads on spleen and symptom end points; momelotinib offers a unique and reproducible TI benefit in anemic patients; and pacritinib fills a critical therapeutic gap in severe thrombocytopenia. These findings support a precision-based, biomarker-informed treatment selection strategy, with anemia and platelet count serving as primary decision variables."

Retrospective data • Review • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

A Study to Assess the Effectiveness and Safety of Pacritinib in Patients With VEXAS Syndrome (PAXIS) (clinicaltrials.gov) - P2 | N=156 | Active, not recruiting | Sponsor: Swedish Orphan Biovitrum | Recruiting ➔ Active, not recruiting

Enrollment closed