Inrebic (fedratinib) / BMS - LARVOL DELTA

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

Therapeutic targeting of ADAR1 p150 splicing activity impairs CD44+ TNBC cell populations in preclinical studies (AACR 2026) - "Rebecsinib selectively reduces CD44+ and ADAR1+ TNBC cell populations and inhibits tumor progression in humanized preclinical models. These findings support further evaluation of Rebecsinib alone and in combination, as a targeted therapeutic approach for TNBC.Keywords: TNBC, ADAR1, CD44, Rebecsinib, targeted therapy, preclinical models."

Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ADAR

In vitro and in vivo screening platform for discovery of JAK2 inhibitors (AACR 2026) - "We established integrated in vivo and in vitro screening platforms for the discovery and evaluation JAK2 inhibitors. This model provides a valuable tool for optimizing treatment regimens against JAK2-driven pathologies."

Preclinical • Essential Thrombocythemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • STAT5

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

Integrative In Silico Multi-Omics Profiling of circRNA-Mediated ceRNA Networks Reveals Prognostic Biomarkers and Repurposed Therapeutic Candidates in Gastric Cancer. (PubMed, Int J Mol Sci) - "To explore therapeutic implications, transcriptomics-guided drug repositioning combined with molecular docking analysis identified five candidate compounds-celastrol, fedratinib, pevonedistat, tozasertib, and withaferin A-predicted to target key network hubs. Overall, this in silico study provides a ceRNA-centered regulatory framework for GC and prioritizes biologically informed biomarkers and repositioned drug candidates with potential applicability across other malignancies to converge precision oncology."

Biomarker • Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • COL4A1 • IGF2BP3 • MMP14 • TGM2

MARKET SHARE AND ECONOMIC TRENDS OF JANUS KINASE INHIBITORS IN U.S. MEDICAID, 2011- 2023 (ISPOR 2026) - "This study describes utilization, spending, pricing, and market share of Medicaid-reimbursed JAK inhibitors (tofacitinib, upadacitinib, baricitinib, ruxolitinib, fedratinib, abrocitinib, ritlecitinib, momelotinib, and deucravacitinib) in the U.S. from 2011-2023. A retrospective descriptive analysis was conducted using the CMS Medicaid outpatient State Drug Utilization Data (2011-2023) for all FDA-approved JAK inhibitors reimbursed by Medicaid. Medicaid JAK utilization and spending increased over time, while market share shifted from Tofacitinib toward newer agents. Price growth among several high-cost agents, alongside market diversification, highlights continuing affordability concerns."

Medicaid • Reimbursement • US reimbursement • Immunology • Inflammation

Fedratinib in combination with CC-486, an oral hypomethylating agent, in Patients with accelerated Phase myelofibrosis: Results from the phase I/II multicenter FAMy trial (DRKS00030348) (DKK 2026) - "For the first time, the feasibility of combining 300mg FED with CC-486 in MPN-AP is shown. Considering the dismal prognosis and lack of optimal therapies for MPN-AP, the encouraging results of this trial warrant further evaluation."

Clinical • Combination therapy • P1/2 data • Hematological Disorders • Infectious Disease • Myelofibrosis

Inhibition of UDP-glucuronosyltransferases by Fedratinib, Implying a High Risk of Drug-drug Interactions. (PubMed, Chem Biol Interact) - "Fedratinib is the second drug approved by the FDA for adult patients with myelofibrosis (MF) following ruxolitinib; however, the mechanism of its dose-limiting toxicity, particularly hepatotoxicity, remains poorly unclear. The results of risk assessment indicated that clinically relevant doses of fedratinib could significantly increase the area under curve (AUC) of drugs mainly metabolized by UGT1A1 and UGT1A3, suggesting a potential risk of clinically significant drug-drug interactions (DDIs). The current research provides useful information for the possible hepatotoxicity mechanism and clinical safe medication of fedratinib."

Journal • Hepatology • Liver Failure • UGT1A3 • UGT2B15

Thiamine transporter 2 and Janus kinase 2 inhibitor, fedratinib suppresses thermogenic activation of human neck area-derived adipocytes. (PubMed, Front Endocrinol (Lausanne)) - "Intriguingly, glutamate transporter (GLT) 1 and L-amino acid transporter (LAT) 2 expression was also attenuated by fedratinib, restricting amino acid consumption. Finally, we found that the expression of ThTr2 in human white adipose tissue was inversely correlated with body mass index, waist-hip ratio, leptin secretion, and plasma insulin, glucose, cholesterol, and triacylglycerol levels, supporting the importance of thiamine metabolism in adipocyte and metabolic health."

Journal • IL12A • JAK2 • LEP

Targeting pathogenic Th2 TRMs formed after early life respiratory viral infection mitigates asthma pathology. (AAAAI 2026) - "Th2 TRMs were specifically targeted with fedratinib, a selective JAK2 inhibitor... Targeting Th2 TRMs formed after early life viral infections mitigates asthma pathology in the setting of virus-induced wheeze. Future studies could further explore targeting these cells in a translational or clinical approach in children with recurrent wheeze and asthma."

Asthma • Immunology • Infectious Disease • Respiratory Diseases

Tartrate-Resistant Acid Phosphatase 5 (TRAP/ACP5) aggravates atherosclerosis by regulating macrophage polarization and promoting ferroptosis. (PubMed, Free Radic Biol Med) - "This ox-LDL-induced upregulation of ACP5 was effectively reversed by the JAK2 inhibitor fedratinib...Conditional ablation of ACP5 significantly reduced aortic plaque area, decreased M1 macrophage proportion in peritoneal lavage fluid, diminished 4-HNE expression in the aortic root, reduced numbers of atrophic mitochondria, and increased aortic GPX4 expression. In conclusion, ACP5 exacerbates atherosclerosis by modulating macrophage polarization and promoting macrophage ferroptosis."

Journal • Atherosclerosis • Cardiovascular • Oncology • Solid Tumor • APOE • GPX4 • TRAP • VDAC3

BRD4-mediated ER membrane contact creates functionally distinct mitochondrial subtypes. (PubMed, Mol Cell) - "Comparison of fedratinib activity to other reported inducers of ERMCSs revealed common mechanisms of induction and function, providing clarity to a growing body of experimental observations. In total, our results uncovered a novel epigenetic signaling pathway and an endogenous metabolic regulator that connects ERMCSs and cellular metabolism."

Journal • BRD4

Post-FDA Approval Experience With Momelotinib in JAK Inhibitor-Naïve Myelofibrosis: Focus on Anemia Response and Treatment-Emergent Nephropathy and Peripheral Neuropathy. (PubMed, Am J Hematol) - "Real-world experience using momelotinib as first-line JAK2 inhibitor therapy in myelofibrosis. Anemia response was moderate (23%) while treatment-emergent adverse events included nephropathy (29%) and peripheral neuropathy (20%)."

FDA event • Journal • Anemia • Hematological Disorders • Myelofibrosis • Pain • Renal Disease

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

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

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

Sodium butyrate induces apoptosis enhanced by JAK2 inhibitor Fedratinib in NK/T-cell lymphoma cell. (PubMed, Clin Transl Oncol) - "NaB effectively promotes apoptosis and inhibits the JAK/STAT signaling pathway in NKTCL, which is further promoted by the JAK2 inhibitors fedratinib. Furthermore, NaB induces EBV reactivation and lytic infection in NKTCL, suggesting its ability to transition EBV from a latent to a lytic form."

Journal • Epstein-Barr Virus Infections • Hematological Malignancies • Infectious Disease • Lymphoma • Natural Killer/T-cell Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma

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

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

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

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

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

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

Journal • Myelofibrosis

Esculentoside a attenuates airway inflammation in asthma by regulating mitochondrial apoptosis via the JAK2/STAT3 pathway. (PubMed, Allergol Immunopathol (Madr)) - ": EsA ameliorates OVA-induced airway inflammation in mice, likely by suppressing the JAK2/STAT3 signaling pathway and attenuating mitochondrial-dependent apoptosis. These findings suggest that EsA holds therapeutic potential as a novel anti-asthmatic agent targeting inflammatory and mitochondrial pathways."

IO biomarker • Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • BAX • BCL2 • CASP3 • IL13 • IL4