Inrebic (fedratinib) / BMS - LARVOL DELTA

Updated Analysis of Overall Survival With Imetelstat in Relapsed or Refractory Myelofibrosis From IMbark Versus Real-World Data and Assessment of Real-World Treatment Patterns: Updated Post Hoc Analysis With Extended Follow-Up (SOHO 2026) - P2 | "RW treatment patterns, baseline/disease characteristics, and mOS of patients diagnosed before/after 2016 (cut point selected to match diagnosis period of IMbark population) and 2019 (fedratinib US approval) were compared. A more favorable OS benefit with imetelstat versus BAT in RW patients with R/R myelofibrosis and poor prognosis was observed. The significant improvement in OS in RW patients over the last decade was independent of transplant status, potentially due to shorter time from diagnosis to ruxolitinib start and earlier switch to next-line JAKi or clinical trial. Evolving treatment patterns are key considerations for interpreting future clinical trial outcomes."

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

Safety and Efficacy of Fedratinib in Patients with Primary (P), Post-Polycythemia Vera (Post-PV), and Post-Essential Thrombocythemia (Post-ET) Myelofibrosis (MF) Previously Treated with Ruxolitinib: Primary Analysis of the FREEDOM Trial (ASH 2022) - P2, P3b | "Clinically relevant and durable spleen and symptom responses were observed in FREEDOM study participants, with a majority of responders showing durable SVR at data cutoff. This supports the use of fedratinib in pts with MF previously treated with RUX. One limitation of the study was small pt sample size."

Clinical • Anemia • CNS Disorders • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Myelofibrosis • Myeloproliferative Neoplasm • Novel Coronavirus Disease • Oncology • Polycythemia Vera • Thrombocytopenia • Thrombocytosis

A Phase 2 Study of Fedratinib in Patients with MDS/MPN and Chronic Neutrophilic Leukemia (ASH 2023) - P2 | "The JAK1/JAK2 inhibitor, ruxolitinib, has shown clinical benefit in pts with MDS/MPN and pts harboring CSF3R mutations. Fedratinib demonstrates promising clinical efficacy in MDS/MPN and CNL pts with proliferative features. The safety profile is consistent with prior experience. Fedratinib's unique kinase inhibition profile may provide a mechanism for enhanced effectiveness in this pt population."

Clinical • P2 data • Anemia • Atypical Chronic Myeloid Leukemia • Chronic Myeloid Leukemia • Chronic Neutrophilic Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Neutropenia • Thrombocytosis • BRD4 • CSF3R • FLT3 • MYC

IO-202, a Novel Anti-LILRB4 Antibody, with Azacitidine for Hypomethylating Agent-Naive Chronic Myelomonocytic Leukemia: Phase 1b Expansion Cohort Results (ASH 2024) - P1 | "Five patients had prior therapies including 4 with hydroxyurea and 1 with fedratinib. Translational data suggest LILRB4 expression as a biomarker for response to therapy, supporting the mechanism of action for IO-202. In light of the paucity of effective therapies for CMML, these data support a future pivotal study of IO-202 + AZA in HMA-naïve CMML."

P1 data • Anemia • Chronic Myelomonocytic Leukemia • Dermatology • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Pruritus • ASXL1 • LILRB4 • RUNX1 • SRSF2 • TET2

MOMENTUM: Phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. (ASCO 2022) - P3 | "Prior JAKi was ruxolitinib in 195 pts (100%) and fedratinib in 9 pts (5%). In symptomatic and anemic MF pts, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need, particularly in MF pts with anemia."

Clinical • P3 data • Anemia • Hematological Disorders • Infectious Disease • Myelofibrosis • Pain • Thrombocytopenia • ACVR1 • JAK1 • 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

Efficacy and Safety of Fedratinib in Patients with Myelofibrosis and Low Baseline Platelet Counts in the Phase 3 Randomized FREEDOM2 Trial (ASH 2024) - P2, P3 | "Introduction Fedratinib (FEDR), a Janus kinase inhibitor (JAKi), demonstrated spleen volume reduction (SVR) and symptom reduction in the phase 3, randomized, open-label FREEDOM2 trial (NCT03952039) vs best available therapy (BAT) in patients (pts) with myelofibrosis (MF) previously treated with ruxolitinib (Harrison CN, et al. Safety was consistent with previous trials. Together, these data suggest a platelet sparing effect of second-line FEDR vs BAT, and support FEDR as a promising second-line treatment option for pts with MF with low or high BL PLT."

Clinical • P3 data • Anemia • Hematological Disorders • Myelofibrosis • Thrombocytopenia

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

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

JAK inhibition in a kidney transplant recipient with primary myelofibrosis (TTS 2026) - "Induction immunosuppression included basiliximab and methylprednisolone, followed by maintenance tacrolimus and mycophenolate mofetil, with dose reduction due to PMF...Subsequently, the patient developed biopsy-proven allograft rejection leading to ruxolitinib discontinuation and transition to the second-generation JAK inhibitor, fedratinib... This case illustrates the complexity of managing concurrent JAK inhibitor therapy and transplant immunosuppression. As JAK inhibitors become more widely used, careful titration of overall immunosuppressive burden, multidisciplinary collaboration, and close virological and graft monitoring will be increasingly important. Whilst further experience is needed to guide their safe use in transplant recipients."

Clinical • Glomerulonephritis • IgA Nephropathy • Immunology • Infectious Disease • Myelofibrosis • Nephrology • Solid Organ Transplantation • Transplant Rejection • Transplantation

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

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

STAT3 Targeting in Brain Metastases: Pharmacokinetic Barriers to JAK/STAT3 Inhibition (EANO 2026) - "However, whether effective STAT3 inhibition can be achieved within the brain metastatic microenvironment at clinically relevant drug exposures remains unclear. We systematically evaluated the brain penetration and transporter affinity of five FDA-approved JAK inhibitors (baricitinib, fedratinib, ruxolitinib, tofacitinib, and upadacitinib) using in vitro transporter assays and in vivo pharmacokinetic studies in wild-type and ABCB1/ABCG2-deficient mice...At clinically relevant exposures in wild-type mice, neither compound meaningfully inhibited STAT3 phosphorylation in tumor cells or reactive astrocytes, even in the presence of the pharmacological ABCB1/ABCG2 inhibitor elacridar. Approved JAK/STAT3 inhibitors lack the pharmacokinetic properties required to achieve sufficient STAT3 target engagement in the brain metastatic microenvironment at clinically relevant exposures. These findings highlight the critical need to incorporate BBB transport and human-relevant exposure..."

PK/PD data • Breast Cancer • Melanoma • Oncology • Solid Tumor • ABCB1 • ABCG2

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

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

BMS-986158, a Potent BET Inhibitor, in Combination with Ruxolitinib or Fedratinib in Patients (pts) with Intermediate- or High-Risk Myelofibrosis (MF): Updated Results from a Phase 1/2 Study (ASH 2023) - P1/2 | "The reductions observed in JAK2 VAF provide promising preliminary data of potential disease modification. Dose expansion with BMS-986158+RUX in 1L MF has opened and is actively enrolling patients."

Clinical • Combination therapy • P1/2 data • Anemia • Cardiovascular • Hematological Disorders • Hepatology • Herpes Zoster • Hypertension • Leukopenia • Myelofibrosis • Neutropenia • Thrombocytopenia • Varicella Zoster • CD34 • JAK2

MOMENTUM: PHASE 3 RANDOMIZED STUDY OF MOMELOTINIB (MMB) VERSUS DANAZOL (DAN) IN SYMPTOMATIC AND ANEMIC MYELOFIBROSIS (MF) PATIENTS PREVIOUSLY TREATED WITH A JAK INHIBITOR (EHA 2022) - P3 | "Prior JAKi was ruxolitinib in 195 pts (100%) and fedratinib in 9 pts (5%); mean duration of prior JAKi was 134 weeks. MMB may address a critical unmet need, particularly in MF pts with anemia. NCT04173494."

Clinical • P3 data • Anemia • Hematological Disorders • Infectious Disease • Myelofibrosis • Pain • Thrombocytopenia • ACVR1

A phase 2 study of canakinumab in patient with myelofibrosis: Results from part 1 (ASH 2025) - "Introduction Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) for which the only approved therapies are JAKinhibitors which improve splenomegaly and disease-related symptoms. Given the encouraging impact onMF symptoms, blood counts and reassuring safety profile, the study was amended to enroll pts on astable dose of a JAK inhibitor (ruxolitinib, fedratinib, momelotinib, or pacritinib) who have the potential tobenefit from additional therapy. Part 2 is currently enrolling at multiple sites and updated clinical andcorrelative data will be presented at the meeting."

Clinical • P2 data • Cardiovascular • Fibrosis • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • CRP • IL1B

Pacritinib Is a Potent ACVR1 Inhibitor with Significant Anemia Benefit in Patients with Myelofibrosis (ASH 2022) - "The subgroup of BAT that received erythroid support (erythropoiesis stimulating agents, danazol, thalidomide or analogs, or corticosteroids) was also analyzed...The inhibitory activity of pacritinib, momelotinib, fedratinib, and ruxolitinib against ACVR1 was assessed using a HotSpot assay (Reaction Biology Corporation)... Baseline characteristics of patients who were not TI (SIMPLIFY criteria) were similar between pacritinib (n=42) and BAT (n=44), including median hemoglobin (8.7 vs. 8.6 g/dL), median platelet count (43 vs. 41 x109/L), and percentage who received prior JAK2 inhibitor therapy (55% vs."

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

A Phase 2 Study of Fedratinib in Patients with MDS/MPN and Chronic Neutrophilic Leukemia (ASH 2024) - P2 | "The JAK1/JAK2 inhibitor, ruxolitinib, has shown clinical benefit in pts with MDS/MPN and pts harboring CSF3R mutations. The safety profile is consistent with prior experience. Fedratinib's unique kinase inhibition profile may provide a mechanism for enhanced effectiveness in this pt population."

Clinical • P2 data • Anemia • Atypical Chronic Myeloid Leukemia • Chronic Myeloid Leukemia • Chronic Neutrophilic Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Neutropenia • Oncology • Thrombocytosis • BRD4 • CALR • CSF3R • FLT3 • MYC

Fedratinib for patients with myelofibrosis - Authors' reply. (PubMed, Lancet Haematol) - No abstract available

Journal • Myelofibrosis

Inflammatory and Immune Microenvironment in Myeloproliferative Neoplasms: Pathogenic Mechanisms and Therapeutic Opportunities. (PubMed, Cancers (Basel)) - "Although FDA-approved JAK1/JAK2 inhibitors ruxolitinib, fedratinib pacritinib and momelotinib effectively reduce splenomegaly and symptom burden and have demonstrated survival benefits in clinical trials, their ability to eliminate malignant clones or induce durable disease modification remains limited, and disease progression continues to occur in most patients. Finally, this review assesses the complex immunological dysfunction and chronic inflammatory dysregulation that characterize Ph-negative MPNs, as well as emerging therapeutic strategies, emphasizing the importance of fully understanding these intricate microenvironmental mechanisms for the identification and development of novel precision treatment targets."

Journal • Review • Cardiovascular • Essential Thrombocythemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytosis • Thrombosis • CALR

Janus kinase inhibitors after ruxolitinib failure in myelofibrosis: A systematic review and pooled analysis of phase 3 efficacy and integrated safety across clinical trials and real-world evidence. (PubMed, Br J Haematol) - "Pooled ≥35% spleen volume reduction at week 24 was 32.7% (95% confidence intervals 27.3-38.6) for fedratinib, 15.8% (11.7-21.0) for momelotinib and 21.6% (13.8-32.3) for pacritinib 200 mg bis in die; pooled ≥50% Total Symptom Score reduction rates were 32.8% (27.4-38.7), 25.3% (20.2-31.3) and 32.4% (22.9-43.7) respectively. Real-world evidence from five momelotinib cohorts (n = 580) identified nephrotoxicity (glomerular filtration rate decline 17%-29%) and peripheral neuropathy (4%-20%) as monitoring targets. Despite limitations from differing study designs, each post-ruxolitinib JAKi shows a distinct efficacy/safety fingerprint mapping onto a phenotype, guiding second-line choice by clinical factors and prior adverse events."

HEOR • Journal • P3 data • Real-world evidence • Retrospective data • Review • Hematological Disorders • Myelofibrosis • Pain

JAKARTA: Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis (clinicaltrials.gov) - P3 | N=289 | Terminated | Sponsor: Bristol-Myers Squibb | Completed ➔ Terminated

Trial termination • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis