Ojjaara (momelotinib) / GSK - LARVOL DELTA

Indirect treatment comparison of momelotinib vs fedratinib safety in patients with myelofibrosis. (PubMed, Future Oncol) - "Risk of any-grade or grade 3/4 anemia, diarrhea, nausea, and treatment-emergent AEs leading to dose reductions was lower with momelotinib in both populations; any-grade thrombocytopenia was also significantly less likely in JAK inhibitor - naive patients. Momelotinib showed a favorable safety profile vs fedratinib, including significantly lower risks of key hematologic and gastrointestinal AEs - such as anemia, diarrhea, and nausea - over 24 weeks."

Journal • Hematological Disorders • Myelofibrosis • Thrombocytopenia

Indirect treatment comparisons of momelotinib vs pacritinib safety and anemia outcomes in patients with myelofibrosis. (PubMed, Future Oncol) - "Momelotinib-treated patients also had greater odds/possibility of hemoglobin improvement of ≥ 1 g/dL and clinical improvement in hemoglobin. Momelotinib provides a more favorable safety profile and a higher chance for hemoglobin improvement vs pacritinib."

Journal • Anemia • Hematological Disorders • Myelofibrosis

Cost-Effectiveness Analysis of Momelotinib for the Treatment of Adult Patients With Myelofibrosis and Anemia in Canada (ISPOR 2025) - "These results suggest that momelotinib is cost-effective vs ruxolitinib/BAT for Canadian patients with myelofibrosis and anemia. Momelotinib-treated patients spent more time in the TI state, which was associated with improved QALYs and may provide cost savings from a Canadian healthcare payer perspective."

Clinical • Cost effectiveness • HEOR • Anemia • Hematological Disorders • Myelofibrosis

IMproveMF: A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination With Ruxolitinib in Participants With Myelofibrosis (clinicaltrials.gov) - P1 | N=51 | Recruiting | Sponsor: Geron Corporation | Trial completion date: Aug 2027 ➔ Aug 2028 | Trial primary completion date: Feb 2026 ➔ Feb 2027

Trial completion date • Trial primary completion date • Myelofibrosis

Emerging Therapeutic Approaches for Anemia in Myelofibrosis. (PubMed, Curr Hematol Malig Rep) - "The pathobiology of anemia is multifactorial, including progressive bone marrow fibrosis, decreased erythropoiesis due to high hepcidin levels leading to iron sequestration in the reticuloendothelial system, hypersplenism, erythropoiesis inhibition by myelosuppressive JAK inhibitors (ruxolitinib, fedratinib), and others...Conventional agents to manage anemia include erythropoiesis-stimulating agents, danazol, corticosteroids, and immunomodulatory agents, but responses are infrequent and lack durability...Momelotinib and pacritinib (ACVR1/JAK2 inhibitor) are the preferred JAK inhibitors for patients with cytopenias (anemia, thrombocytopenia). Luspatercept and elritercept are activin receptor ligand traps, promoting erythroid maturation and late-stage erythropoiesis...DISC-0974 is a first-in-class anti-hemojuvelin (positive hepcidin regulator) monoclonal antibody that decreased hepcidin expression, increased serum iron, and enhanced erythropoiesis in anemic patients with..."

Journal • Review • Anemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ACVR1

Importance of starting treatment early with momelotinib which may impact survival in myelofibrosis patients (GSK Press Release) - "At EHA 2025, new analyses from the pivotal MOMENTUM and SIMPLIFY-1 trials reinforce momelotinib as a standard of care in myelofibrosis (MF), The data explore the benefits of initiating treatment for myelofibrosis earlier, which could lead to better outcomes for patients. Presentations include: (i) New post-hoc analyses from the MOMENTUM & SIMPLIFY-1 trials show addressing anaemia and achieving haemoglobin improvement of 10 g/dL or above may positively impact overall survival (EHA abstract #PF828); (ii) New SIMPLIFY-1 subgroup data show the impact of patients achieving both ≥ 35% spleen volume reduction (SVR35) and transfusion independence responses with momelotinib, which are prioritised in treatment guidelines to support optimal long-term outcomes in patients (EHA abstract #PS1829)."

P3 data • Myelofibrosis

ODYSSEY: Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: GlaxoSmithKline | Phase classification: P1/2 ➔ P2

Phase classification • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis

Momelotinib - a tale of trials, tribulations, transfusion independence, and triumph. (PubMed, Expert Opin Drug Discov) - "The development of momelotinib represents an important breakthrough in MF therapy with spleen and symptom directed therapy with improvements in anemia and limited myelosuppression, facilitating dose intensity. Current and future research efforts for MF therapy are directed at development of newer, anemia-directed therapies including combinations with momelotinib."

Journal • Review • Hematological Disorders • Myelofibrosis • ACVR1 • JAK1

EFFICACY OF PACRITINIB VS MOMELOTINIB IN PATIENTS WITH THROMBOCYTOPENIC MYELOFIBROSIS: A MATCHED ADJUSTED INDIRECT TREATMENT COMPARISON (EHA 2025) - P3 | "This MAIC revealed a consistent, nominal trend towards PAC benefit across all efficacy endpoints and OS as evaluated in patients with TMF, most of whom had moderate thrombocytopenia. When comparing therapies across disparate trials with differences in study design, it is essential to account for differences (including those of study populations) by adjusting for effect modifiers. Importantly, this analysis accounted for key baseline patient prognostic differences to ensure balanced analytic populations between the trials."

Clinical • Anemia • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1 • JAK1

TRIAL IN PROGRESS: MIDAS - A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF MOMELOTINIB IN PATIENTS WITH ANEMIA DUE TO LOWER-RISK MYELODYSPLASTIC SYNDROMES (EHA 2025) - P2 | "First-line treatments include erythropoiesis-stimulating agents (ESAs) or luspatercept, and imetelstat is a second-line option following ESAs...Patients may enroll regardless of ring sideroblast status, while those with del5q cytogenetic abnormalities are ineligible regardless of prior lenalidomide exposure.In part 1 (Figure), 40 patients will be stratified by baseline transfusion burden (≤6 vs >6 units in 8 weeks) and randomized 1:1 to 1 of 2 momelotinib dose levels to establish the RP2D, at which up to 40 patients will be enrolled in part 2... This will be the first clinical study of momelotinib in patients with LR-MDS and anemia. Part 1 enrollment is planned to begin in April 2025."

Clinical • P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • IRAK1 • JAK1 • JAK2

CLINICAL DETERMINANTS OF HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH JANUS KINASE INHIBITOR-EXPERIENCED MYELOFIBROSIS (EHA 2025) - P3 | "SIMPLIFY-2 (NCT02101268) was an open-label, phase 3 trial of momelotinib (n=104) vs best available therapy (ruxolitinib in 88.5% of patients; n=52) in patients with intermediate- or high-risk MF previously treated with ruxolitinib. In this JAK inhibitor-experienced trial population, transfusion status was the strongest predictor of HRQOL, with the three endpoints highly correlated. These results highlight the clinical importance of achieving transfusion independence and support the use of clinical endpoints in defining HSUVs in MF."

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

EVALUATING INTERVENTIONAL TRIALS IN MYELOFIBROSIS-ASSOCIATED ANEMIA: A SYSTEMATIC LITERATURE REVIEW OF BASELINE ANEMIA STATUS AND TRANSFUSION INDEPENDENCE OUTCOMES (EHA 2025) - "Among the limited number of groups with reported baseline RBCT status (n=6), the TI rate was 14% in patients receiving ≤1 unit/month (ruxolitinib), 29-36% in those receiving 1-2 units/month (momelotinib), and 16-26% in those receiving 2-3 units/month (luspatercept and pomalidomide). This analysis examined the definitions of baseline anemia severity utilized in interventional trials and associated clinical outcomes in patients with MF-related anemia. Inclusion criteria for defining baseline transfusion burden varied based on Hgb thresholds, the number of transfused units, and the time period. Despite many MF patients becoming TD due to disease progression and treatment with JAKi, few trials focused on this hard-to-treat population, and treatment options remain limited for patients with a high transfusion burden."

Review • Anemia • Hematological Disorders • Myelofibrosis

IMPACT OF DUAL SPLEEN RESPONSE AND TRANSFUSION INDEPENDENCE ON SURVIVAL IN JAK INHIBITOR-NAIVE PATIENTS WITH MYELOFIBROSIS AND ANEMIA TREATED WITH MOMELOTINIB: A SUBGROUP ANALYSIS OF SIMPLIFY-1 (EHA 2025) - "In this trial population of JAK inhibitor-naive patients with baseline Hb <10 g/dL, momelotinib provided comparable SVR to ruxolitinib across most patient subgroups. Most patients achieved dual SVR35+TI responses with momelotinib, illustrating its combined benefits for spleen reduction and anemia in MF, while similar SVR35 rates with ruxolitinib often resulted in transfusion need. TI emerged as the strongest predictor of OS with momelotinib, suggesting that this endpoint should be prioritized in anemic patients with MF to optimize long-term outcomes."

Clinical • Anemia • Hematological Disorders • Myelofibrosis

NEUTROPHIL EXTRACELLULAR TRAPS (NETS) IN MYELOPROLIFERATIVE NEOPLASMS (MPNS): IMPACT OF CYTOREDUCTIVE THERAPY (EHA 2025) - "Among the 26 patients who showed a decrease they comprised 10 out of 15 patients treated with Ruxolitinib, compared to 6 out of 11 on Hydroxycarbamide, 6 out of 10 on Pegylated-Interferon, and 4 out of 6 on Momelotinib. H3.1 nucleosome levels varied across MPN subtypes, with higher concentration observed in MF. Prior antiaggregant therapy was associated with lower levels. Cytoreductive therapy reduced H3.1 nucleosome levels in 62% of patients, with the greatest decrease in PV."

Cardiovascular • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombosis • CALR

ANEMIA RESPONSE IN PATIENTS WITH MYELOFIBROSIS TREATED WITH LUSPATERCEPT: A REAL-WORLD COHORT STUDY (EHA 2025) - "The majority of patients (80%) were treated with a combination of JAK inhibitor with luspatercept; Ten (67%) patients received concomitant ruxolitinib, and 2 (13%) received concomitant momelotinib. Response rates in this real-world cohort of largely secondary MF treated with the luspatercept and JAK inhibitor combination are encouraging, despite the small sample size. Further dose optimization and identification of predictive response metrics are essential to better tailor luspatercept use for anemia in MF patients."

Clinical • Real-world • Real-world evidence • Anemia • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis • CALR • JAK2 • TET2

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

MYMPNVOICE APP: REMOTE LONGITUDINAL MONITORING OF PATIENT REPORTED OUTCOMES AND BIOMETRICS IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS (EHA 2025) - "Uniquely concerning linked biometric data, we report that higher TSS were significantly associated with lower activity levels across the entire cohort and all MPN subtypes (p<0.05).Concerning treatment correlations: In ET TSS was 16.2 in hydroxycarbamide (HC) treated patients (HC, n=41), 14.2 with pegylated interferon (IFN, n=39) and 12.5 on active surveillance (AS, n=45) (all comparisons p<0.05)...In PV TSS was 21.0 in patients treated with ruxolitinib (RUX, n=16), 16.2 with IFN (n=27), 12.7 with HC (n=36), and 8.3 on AS (n=28) (all comparisons p<0.05)...In MF TSS was 17.3 in patients treated with HC (n=5),13.9 with momelotinib (MMB, n=6), 13.3 on AS (n=13), 10.7 with RUX (n=14) and 9.7 with IFN (n=6)... In this unique ongoing study, we have shown important correlation between TSS and activity levels suggesting the latter could form the basis of an objective future trial endpoint. This work supports the feasibility of longitudinal digital health data modelling..."

Clinical • Patient reported outcomes • CNS Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Sleep Disorder • CALR • JAK2

PRELIMINARY DATA FROM PHASE I/II STUDY OF NUVISERTIB, AN ORAL INVESTIGATIONAL SELECTIVE PIM1 INHIBITOR, SHOWED CLINICAL RESPONSE CORRELATING WITH CYTOKINE MODULATION IN PATIENTS WITH MYELOFIBROSIS (EHA 2025) - P1/2 | "Nuvisertib monotherapy appeared well tolerated with no DLTs. Preliminary data showed clinical activity including SVR25, symptom improvement correlating with cytokines modulation, BM fibrosis reduction, and Hgb and PLT responses in relapsed/refractory (R/R) MF pts. Emerging data support clinical development of nuvisertib in combination with JAK inhibitors ruxolitinib and momelotinib (NCT04176198, Arms 2 and 3, respectively)."

Clinical • P1/2 data • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Myelofibrosis • Oncology • Thrombocytopenia • PIM1

Physiological roles and therapeutic implications of USP6. (PubMed, Cell Death Discov) - "A number of potential small molecule inhibitors are known to be responsible for suppression of USP6, such as Momelotinib (CYT387), FT385, USP30 Inh-1, -2 and -3, 2,6-Diaminopyridine-3,5-bis(thiocyanate) (PR-619) and so on. This review explores the emerging role of USP6 as a key regulator of cellular signaling pathways, its involvement in disease progression, its physiological functions, and the inhibitors that effectively suppress USP6 activity in detail. The comprehensive study provides insight to enhance our understanding of biological importance and therapeutic interventions of USP6 in drug development."

Journal • Review • Breast Cancer • CNS Disorders • Colorectal Cancer • Oncology • Osteosarcoma • Solid Tumor • Targeted Protein Degradation • USP6

Momelotinib in JAK2 inhibitor-naïve myelofibrosis: pros and cons. (PubMed, Blood Cancer J) - No abstract available

Journal • Myelofibrosis

JAK Inhibitor Therapy in the Myeloproliferative Neoplasm Population: Episode 17 Considering Therapy in a Patient With Myelofibrosis Eligible for Transplant (Targeted Oncology) - "Saurabh Chhabra, MD: I agree with you. I don't think there are any data suggesting that we should use only one particular JAK inhibitor. Most of the experience that we have is with ruxolitinib, but we're seeing more and more experience with pacritinib now. At the end of the day, we want to control the symptoms, reduce the spleen size, and buy more time so that we have a donor available and have the comorbidities managed properly, and have some sort of response to the treatment. I don't care what treatment was chosen for the patient, whether it's momelotinib, fedratinib, or pacritinib."

Media quote

Are Jak Inhibitors Contributing to Ototoxicity? Investigating Their Role in Aminoglycoside-Induced Damage (COSM 2025) - "C57BL/6J Cdh23-corrected mice were treated with JAK inhibitors (momelotinib 20 mg/kg, tofacitinib 20 mg/kg, upadacitinib 10 mg/kg) via oral gavage for 14 days, alone or combined with kanamycin (600 mg/kg, S.C.). Systemic administration of JAK inhibitors enhances the ototoxic effects of kanamycin, emphasizing the role of the JAK-STAT pathway in auditory protection. JAK2 knockout mice were particularly vulnerable to aminoglycoside-induced hearing loss and vestibular dysfunction. These findings highlight a critical role for JAK-STAT signaling in mitigating aminoglycoside ototoxicity, suggesting that patients treated with JAK inhibitors could be at higher risk for hearing loss when exposed to aminoglycosides."

Otorhinolaryngology • CDH23 • JAK2 • PAX2

Real world outcomes of momelotinib in myelofibrosis patients with anemia: results from the MOMGEMFIN study. (PubMed, Blood Cancer J) - No abstract available

Journal • Real-world evidence • Anemia • Hematological Disorders • Myelofibrosis

GSK in breach for misleading prescription information on Omjjara, industry body says (The Economic Times) - "British pharmaceutical giant GSK has not met required ethical and regulatory standards in the marketing and prescription information for its Omjjara drug, an industry self-regulatory body said on Tuesday. Omjjara is used to treat symptoms such as an enlarged spleen in adults with myelofibrosis - a rare bone marrow blood cancer - and moderate to severe anemia. The prescribing information provided for the drug misled women using hormonal contraceptives about the necessity for extra precautions to prevent pregnancy, the Prescription Medicines Code of Practice Authority (PMCPA) said."

Commercial • Myelofibrosis

Managing Myelofibrosis: Matching Advances in Treatments With Clinical Unmet Needs. (PubMed, Hematol Oncol) - "The janus kinase inhibitor (JAKi) ruxolitinib has been the mainstay of treatment for over a decade...Other JAKi (pacritinib, momelotinib, jaktinib) address treatment-related cytopenia, expanding the therapeutic utility of this class of agents to patients with baseline anemia or thrombocytopenia. Novel candidates exploit multiple molecular pathways, and offer the potential to improve the management of MF-associated cytopenia (imetelstat, pelabresib, navitoclax, selinexor, luspatercept, sotatercept, elritercept, LCL161, bomedemstat) and recover bone marrow fibrosis (imetelstat, pelabresib, navitoclax and bomedemstat). It remains to be seen if these newer agents can induce any remission in MF and enable patients to come off therapy, but the future is beginning to look much brighter."

Journal • Review • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia