Ojjaara (momelotinib) / GSK - LARVOL DELTA

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

Momelotinib in VEXAS syndrome: a preliminary report evaluation of safety and effectiveness (ACR Convergence 2026) - No abstract available

Clinical • Inflammation

SURVIVAL IMPACT AND KINETICS OF HEMOGLOBIN IMPROVEMENT WITH MOMELOTINIB IN PATIENTS WITH MYELOFIBROSIS AND MODERATE TO SEVERE ANEMIA: POST HOC ANALYSES OF SIMPLIFY-1 AND MOMENTUM (EHA 2025) - "SIMPLIFY-1 and MOMENTUM were randomized, double-blind, phase 3 trials of momelotinib (n=215) vs ruxolitinib (n=217) in JAK inhibitor-naive patients and momelotinib (n=130) vs danazol (n=65) in JAK inhibitor-experienced patients, respectively. Anemia severity at BL dictates the probability and kinetics of achieving Hb >10 g/dL with momelotinib. Patients with BL moderate anemia were numerically more likely to achieve this threshold and faster than those with BL severe anemia, underscoring the benefits of earlier anemia intervention with momelotinib to maximize clinical outcomes. Regardless of anemia severity, patients who achieved Hb >10 g/dL by week 24 with momelotinib had numerically longer OS than those who did not, validating achievement of Hb levels above this threshold as a positive prognostic factor."

Clinical • Retrospective data • Anemia • Hematological Disorders • Myelofibrosis • ACVR1 • JAK1 • JAK2

RESULTS OF AJX-101, A PHASE 1 CLINICAL TRIAL OF THE TYPE II JAK2 INHIBITOR AJ1-11095, IN PATIENTS WITH MYELOFIBROSIS WHO HAVE BEEN FAILED BY A TYPE I JAK2 INHIBITOR (EHA 2026) - P1 | "Results In the dose escalation phase, 23 patients (ages 47-87y,16M/7F; 16 JAK2 V617F, 6 CALR, 2 MPL W515K/L mutations; median 2 prior therapies (range 1-7), median 6.1y from diagnosis; all with prior ruxolitinib exposure, 8 with momelotinib) enrolled across 6 dose levels: 25 (n=3), 50 (n=3), 75 (n=6), 100 (n=6), and 125 mg (n=5) orally once daily. Summary/Conclusion The first-in-class type II JAK2 inhibitor AJ1-11095 induces symptomatic improvement, spleen volume reduction, and decrease in mutant clone size in most patients with MF previously treated with type I JAK2 inhibitors. The 75 mg QD dose was selected for initial dose expansion."

Clinical • First-in-human • P1 data • Myelofibrosis • Thrombocytopenia • CALR • TYK2

Bone Marrow Fibrosis Changes Do Not Correlate with Efficacy Outcomes in Myelofibrosis: Analysis of More Than 300 JAK Inhibitor-Naïve Patients Treated with Momelotinib or Ruxolitinib (ASH 2022) - "These data represent the most extensive analysis to date of the correlation of BMF changes with other outcome measures in JAKi-naïve patients with MF. Of particular note, anemia improvement was not linked with BMF changes. These findings bring into question the use of BMF assessment at W24 as a surrogate for clinical benefit."

Clinical • Anemia • Hematological Disorders • Immunology • Myelofibrosis • ACVR1

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

Association between hemoglobin (Hb) improvement and patient-reported outcomes (PROs) in patients (pts) with myelofibrosis (MF) and anemia: Post hoc pooled analysis of momelotinib (MMB) phase 3 trials. (ASCO 2024) - P3 | " The pooled treatment-agnostic analysis set included pts with anemia (baseline [BL] Hb <10 g/dL) from 3 phase 3 trials: S1 (JAK inhibitor [JAKi] naive; MMB vs ruxolitinib), S2 (JAKi experienced; MMB vs best available therapy), and MOMENTUM (JAKi experienced; MMB vs danazol). In these trial populations, Hb improvement at wk 24 was associated with improved HRQOL and symptoms in pts with MF and anemia. These results highlight the value of treatments with anemia-related benefits in improving the pt experience in MF."

P3 data • Patient reported outcomes • Retrospective data • Anemia • Hematological Disorders • Myelofibrosis

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

Preliminary data from the Phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, in combination with momelotinib showed clinical responses in patients with relapsed/refractory myelofibrosis (ASH 2025) - P1/2 | "Nuvisertib (NUVI, TP-3654), an oralinvestigational highly selective PIM1 kinase inhibitor, alone and in combination with ruxolitinib (RUX)showed spleen size reduction and bone marrow (BM) fibrosis improvement in JAK2V617F and MPLW515LMF mouse models. NUVI + MMB combo appeared to be well tolerated. Preliminary data showed early clinicalactivity including 60% TSS50 response and absolute symptom improvement, 40% SVR25 response,cytokine modulation and anemia improvement in R/R MF pts with anemia. Preliminary data supportsfurther development of NUVI + MMB combo for pts with MF."

Clinical • Combination therapy • P1/2 data • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ACVR1 • PIM1

Impact of Transfusion Burden on Health‑Related Quality of Life and Functioning in Patients With Myelofibrosis: Post Hoc Analysis of SIMPLIFY‑1 and ‑2 (SOHO 2023) - "Design: The pooled analysis set comprised both arms of the intent-to-treat populations of SIMPLIFY-1 (JAK inhibitor-naïve, momelotinib vs ruxolitinib; N=432) and SIMPLIFY-2 (JAK inhibitor-experienced, momelotinib vs best available therapy; N=156). Among patients with myelofibrosis in the SIMPLIFY studies, TD patients had lower functioning and HRQOL than TI patients across SF-36v2 domains, suggesting that transfusion dependence negatively affects multiple aspects of QOL. Baseline TD patients who became TI at W24 had greater improvement across most domains than those who remained TD, with mean changes near/above the minimally important differences. These analyses support further research into the impact of transfusions on QOL in myelofibrosis."

Clinical • HEOR • Retrospective data • Myelofibrosis • Oncology • ACVR1 • JAK1 • JAK2

Momelotinib (MMB) Long-Term Safety: Pooled Data from Three Phase 3 Randomized-Controlled Trials (RCTs) (ASH 2022) - " Adult pts with high- and intermediate-risk MF were randomized to receive MMB or ruxolitinib (RUX; S1); MMB or best available therapy, which was RUX in 89% (S2) of patients; and MMB or danazol (MOMENTUM). We report the largest trial safety database to date for a JAK inhibitor in MF. MMB demonstrated a consistent safety profile without unexpected long-term or cumulative toxicity."

Clinical • P3 data • Acute Myelogenous Leukemia • Anemia • Genetic Disorders • Infectious Disease • Myelofibrosis • Neutropenia • Non-melanoma Skin Cancer • Pain • Skin Cancer • Solid Tumor • Thrombocytopenia • ACVR1 • JAK1 • JAK2

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

Momelotinib Long-Term Safety and Survival in Myelofibrosis: Integrated Analysis of Phase 3 Randomized-Controlled Trials. (PubMed, Blood Adv) - "Patients in the control arms (danazol in MOMENTUM; ruxolitinib in SIMPLIFY-1; best available therapy in SIMPLIFY-2) could cross over to receive momelotinib at the end of the 24-week randomized period, and all patients could continue momelotinib treatment after the completion of these studies via an extended access protocol. Incidence of AEs of clinical importance (eg, infections, malignant transformation, peripheral neuropathy, hemorrhage) did not increase over time. This analysis of one of the largest randomized trial databases for a JAK inhibitor to date in myelofibrosis demonstrated a consistent safety profile of momelotinib without long-term or cumulative toxicity."

Journal • P3 data • Infectious Disease • Myelofibrosis • Neutropenia • Pain • Thrombocytopenia • ACVR1 • JAK1 • JAK2

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

Impact of transfusion burden on health-related quality of life (HRQOL) and functioning in patients (pts) with myelofibrosis (MF): Post hoc analysis of SIMPLIFY-1 (S1) and -2 (S2). (ASCO 2023) - P3 | "To characterize the relationship between transfusion burden and pt-reported outcomes (PROs), we report an exploratory post hoc analysis of the phase 3 S1 and S2 trials of the JAK1/JAK2/ACVR1 inhibitor momelotinib (MMB) in pts with MF. The pooled analysis set comprised both arms of the intent-to-treat populations of S1 (JAK inhibitor naive, MMB vs ruxolitinib [RUX]; N = 432) and S2 (JAK inhibitor exposed, MMB vs best available therapy [88% RUX]; N = 156)... Among pts with MF in S1 and S2, TD pts had lower functioning and HRQOL than TI pts across SF-36v2 domains, suggesting that transfusion dependence has detrimental effects on multiple aspects of QOL. Among BL TD pts, those who became TI at W24 had greater improvement across most domains than those who remained TD, with mean changes for TD-TI pts near or above the minimally important difference (2 or 3, based on domain) for groups with low BL NBS. These analyses highlight transfusion dependence as a key pt-centered..."

Clinical • HEOR • Retrospective data • Anemia • Hematological Disorders • Myelofibrosis • ACVR1 • JAK1 • JAK2

Characterization of Symptoms After Immediate Transition From Ruxolitinib to Momelotinib in Patients With Myelofibrosis: Post-Hoc Analyses of the Phase 3 SIMPLIFY-1 and SIMPLIFY-2 Trials (SOHO 2026) - P3 | "Immediate ruxolitinib-to-momelotinib transition is not associated with severe or acute symptom relapses. Events were generally infrequent, low-grade, and transient. These findings inform symptom management expectations during ruxolitinib-to-momelotinib switch in patients with myelofibrosis."

Clinical • P3 data • Retrospective data • Myelofibrosis • Oncology

Preliminary Data From Ongoing Global Phase 1/2 Study of Investigational PIM1 Inhibitor Nuvisertib in Combination With Momelotinib Show Promising Clinical Activity in Patients With Myelofibrosis and Anemia (SOHO 2026) - P1/2 | "According to preliminary data from this ongoing phase 1 dose-escalation study in patients with R/R myelofibrosis and anemia, NUVI+ MMB (fed) appeared to be well tolerated and showed promising clinical activity, including symptom and spleen responses, anemia improvement, and cytokine modulation. Emerging data support further development of the NUVI+ MMB combination (fed) for myelofibrosis. DIPSS: Dynamic International Prognostic Scoring System, JAK, Janus kinase, PIM1: proto-oncogene serine/threonine-protein kinase Pim-1, SVR: spleen volume reduction, TSS: total symptom score."

Clinical • Combination therapy • P1/2 data • Myelofibrosis • Oncology • ACVR1 • IL18

CHARACTERIZATION OF SYMPTOMS AFTER IMMEDIATE TRANSITION FROM RUXOLITINIB TO MOMELOTINIB IN PATIENTS WITH MYELOFIBROSIS: POST HOC ANALYSES OF THE PHASE 3 SIMPLIFY-1 AND SIMPLIFY-2 TRIALS (EHA 2026) - P3 | "Incidence Over Time of AEs Resembling MF Symptoms After Crossover From RUX to Momelotinib in SIMPLIFY-1 (n=88). AE, adverse event; MF, myelofibrosis; RUX, ruxolitinib."

Clinical • P3 data • Retrospective data • Hematological Malignancies • Inflammation • Myelofibrosis • Pruritus

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

The Selective PI3KδInhibitor Roginolisib Synergizes With JAK Inhibitors in Progenitor Cells From Naïve and JAK Inhibitor–Refractory/Resistant Patients With Myelofibrosis (SOHO 2026) - P1/2 | " Roginolisib alone did not inhibit proliferation in JAK2 V617F UKE-1 cells up to 10 μM, whereas ruxolitinib (Ruxo) showed the expected activity...Combinations with Ruxo or momelotinib led to marked, synergistic inhibition of colony formation (CI, 0.07–0.5), reaching ∼70% to 80% suppression... Roginolisib shows activity in primary MF cells and demonstrates strong synergy with JAK inhibitors. These results support the ongoing phase 1b trial of roginolisib in MF patients with suboptimal responses to JAKi (HEMAMED, NCT06887803). AKT: protein kinase B, CALR: calreticulin, CD: cluster of differentiation, CXCL10: chemokine (CX-C motif) ligand, JAK: Janus kinase, JAK2: Janus kinase 2, MPL: MPL proto-oncogene, thrombopoietin receptor, mTOR: mammalian target of rapamycin, PI3K: phosphoinositide 3-kinase."

Clinical • Hematological Malignancies • Myelofibrosis • Oncology • CALR • CD34 • CXCL10 • CXCL8 • IL6 • MPL • PIK3CD • TNFA

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