Ojjaara (momelotinib) / GSK - LARVOL DELTA

Ojjaara (momelotinib) approved in Canada for the treatment of myelofibrosis in adults who have moderate to severe anemia (Canada Newswire) - "GSK announced today that Health Canada has approved Ojjaara (momelotinib) for the treatment of splenomegaly and/or disease-related symptoms, in adult patients with intermediate or high-risk primary myelofibrosis (MF), post polycythemia vera MF or post essential thrombocythemia MF who have moderate to severe anemia....The approval of Ojjaara by Health Canada is supported by data from the pivotal MOMENTUM Phase III trial, which demonstrated significant improvements in Total Symptom Score (TSS), Transfusion Independence, and Splenic Response Rate....Additional support came from a subset of patients in the SIMPLIFY-1 Phase III trial..."

Canada approval • Myelofibrosis

Real-World Outcomes of Momelotinib As an Alternative Therapy to Other JAK Inhibitors in Myelofibrosis Patients with Anemia (ASH 2024) - "Seventy-seven percent of pts had previously received erythropoietin stimulating agents and 11% danazol...The remaining 128 had a median of 1.2 prior lines (range 1-6), with 91% having received ruxolitinib, 3% fedratinib, 21% hydroxyurea, 8.6% corticosteroids, and 4% thalidomide/lenalidomide... Real-life treatment with MMB confirms its marked effect in improving anemia in MF patients, with high rates of patients achieving TI in both iJAK-exposed and iJAK naïve patients. Additionally, MMB has proven effective in reducing symptoms and controlling splenomegaly in pts previously exposed to ruxolitinib, with an acceptable toxicity profile."

Clinical • Real-world • Real-world evidence • Anemia • Anorexia • Bone Marrow Transplantation • Dermatology • Hematological Disorders • Hepatology • Hypotension • Infectious Disease • Myelofibrosis • Nephrology • Pain • Pruritus • Renal Disease • Thrombocytopenia • ACVR1 • ASXL1 • CALR • JAK1 • JAK2 • SRSF2 • U2AF1

Mympnvoice – a Novel Smartphone App for Monitoring Patient Reported Outcomes and Biometric Data in Patients with Myeloproliferative Neoplasms (ASH 2024) - "In ET patients MPN-10 score was 20.3 in patients treated with hydroxycarbamide (HC, n=14), 13.2 with pegylated interferon (IFN, n=15) and 11.5 on active surveillance (AS, n=25) (HC vs IFN, AS p<0.001). In PV patients MPN-10 score was 13.7 in patients treated with HC (n=8), 20.2 in IFN (n=12), 12.1 on ruxolitinib (RUX, n=3) and 13.4 on AS (n=21) (IFN vs HC, RUX, AS p<0.001). In MF patients MPN-10 was 12.9 in patients treated with HC (n=2), 7.1 in IFN (n=1), 6.9 on momelotinib (MMB, n=3), 13.1 on RUX (n=5) and 13.9 on AS (n=8) (MMB vs AS, RUX p<0.001)... At data cut-off (18th July 2024), 139 patients were recruited with median follow-up of 49 days. Median age was 55 years (range 27-80), 63% were female. Patients had a mean daily completion rate of 66% across EQ-5D-5L and MPN-10 PRO measures (range 0-95%)."

Clinical • Patient reported outcomes • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Treatment of Myeloproliferative Neoplasms with Janus Kinase Inhibitors: A Meta-Analysis of Cardiovascular Safety (ASH 2024) - "The analysis of MACE included ruxolitinib (n=8) and pacritinib (n=2); the analysis of hypertension included ruxolitinib (n=4), momelotinib (n=1), and pacritinib (n=1); and the analysis of thrombosis included ruxolitinib (n=8) and momelotinib (n=1). These findings suggest that ruxolitinib significantly reduces the risk of thrombosis in patients with PV and MF and may show a similar effect in ET alongside momelotinib in MF. As thrombosis is a major cause of mortality in MPNs, a reduction in thromboembolic events should be considered an additional clinical benefit of JAK inhibitors. Moreover, our analysis suggests that the use of JAK inhibitors in the treatment of MPNs is not associated with an increase in MACE, adding to the existing body of evidence which demonstrates the safety of JAK inhibitors in the treatment of MPNs."

Retrospective data • Cardiovascular • Congestive Heart Failure • Essential Thrombocythemia • Heart Failure • Hematological Disorders • Hypertension • Immunology • Inflammatory Arthritis • Myelofibrosis • Myeloproliferative Neoplasm • Myocardial Infarction • Oncology • Polycythemia Vera • Rheumatoid Arthritis • Rheumatology • Thrombocytosis • Thrombosis

Post-Approval Utilization of Pacritinib and Momelotinib in Patients with Myelofibrosis and Analysis of Early Treatment Outcomes (ASH 2024) - "In patients treated with MMB, hgb increase from baseline to 3 mo was more marked in those patients who were transitioning from ruxolitinib to MMB compared to patients with no recent ruxolitinib use (≤ 2 mo prior to MMB) (Δhgb 1.42 g/dL vs. 0.42 g/dL). Favorable impacts on anemia and transfusion requirements were shown with both PAC and MMB though long-term follow-up is limited. Ongoing evaluation in a large, multi-center, real world database of PAC and MMB-treated patients may help optimize treatment selection in patients with cytopenic MF."

Clinical • Anemia • Hematological Disorders • Myelofibrosis • Oncology • Thrombocytopenia

Real-World Baseline Characteristics and Preliminary Outcomes in Patients with Myelofibrosis Treated with Momelotinib in the US Community Oncology Practice Setting (ASH 2024) - "JAK inhibitors such as ruxolitinib and fedratinib have shown positive effects on spleen size and symptom burden; however, they do not address and may exacerbate anemia. Most patients with MF and anemia in this US community practice setting had prior JAK inhibitor exposure at the time of momelotinib initiation, highlighting the high medical need in this patient population. Early results demonstrated higher hemoglobin levels and platelet counts after 3 months of treatment, suggesting momelotinib may benefit patients with anemia and thrombocytopenia. These findings provide important real-world insight into the ability of momelotinib to address the clinical needs of patients with MF and anemia and highlight its adaptability to the real-world community oncology practice setting."

Clinical • Real-world • Real-world evidence • Anemia • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Oncology • Thrombocytopenia • ACVR1 • JAK1 • JAK2

Cost-Effectiveness of Momelotinib for Treatment of Myelofibrosis in Taiwan (ISPOR-EU 2024) - "Use of momelotinib versus the blended comparator (i.e., ruxolitinib and BAT) is cost-effective for MF, suggesting momelotinib as an economically rational alternative over existing treatments in Taiwan. FUNDING: GSK (study ID 222785)."

Cost effectiveness • HEOR • Anemia • Hematological Disorders • Myelofibrosis

Crebbp Inhibition Potentiates JAK2 Inhibition in Post-MPN Acute Myeloid Leukemia (ASH 2024) - "Here, we demonstrate through genome-wide CRISPR screens in post-MPN AML line HEL treated with four different JAK2 inhibitors (i.e. ruxolitinib, momelotinib, pacritinib and fedratinib) that depletion of CREBBP sensitizes cells to JAK2 inhibition...In both human and murine models of post-MPN AML, the combination treatment of ruxolitinib plus CREBBP/EP300 inhibitor SGC-CBP30 or CCS1477 substantially induced apoptosis and cell cycle arrest at G1...Overall, our results demonstrate that CREBBP/EP300 inhibition potentiates JAK2 inhibition in post-MPN AML by further attenuating MYC expression and activity, and repressing JAK/STAT and other pathways associated with JAK2 inhibitor persistence. Therefore, we propose CREBBP inhibition as a potential therapeutic strategy to potentiate JAK2 inhibition in post-MPN AML."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • CALR • CREBBP • EP300 • HSF1 • MYC • STAT3 • STAT5

Nuvisertib (TP-3654), an Investigational Selective PIM1 Kinase Inhibitor, Showed Durable Clinical Response and Sustained Hematological Improvement in Relapsed/Refractory Myelofibrosis Patients (ASH 2024) - P1/2 | "TP-3654 monotherapy was well tolerated with no DLTs. Preliminary data of TP-3654 in relapsed/refractory MF pts showed clinical activity including SVR25, symptom improvement correlating with cytokines reduction, BM fibrosis reduction, and Hgb and PLT responses. Current monotherapy and preclinical data support the development of TP-3654 in combination with JAK inhibitors ruxolitinib and momelotinib (NCT04176198, Arms 2 and 3, respectively); enrollment ongoing in all 3 arms."

Clinical • Anemia • Fatigue • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Musculoskeletal Pain • Myelofibrosis • Oncology • Pain • PIM1

Rapid and Sustained Recovery of Cellular Immunity in Patients with Myelofibrosis on Momelotinib Therapy (ASH 2024) - "While established JAKi therapy with Ruxolitinib (RUX) is linked to notable immunosuppression, the impact of MMB on cellular immunity has not yet been studied. We describe a notable recovery in immune cell frequencies as soon as 6 weeks after starting MMB therapy, persisting up to 48 weeks. The degree of contribution from RUX discontinuation remains unclear, however, responses were also observed in a RUX-naïve cohort, suggesting an additional MMB off-target effect. Additionally, we continue to demonstrate that MMB significantly improves anemia and reduces transfusion dependency in a real-world setting."

Clinical • Anemia • Hematological Disorders • Myelofibrosis • ACVR1 • CD4 • CD8

Overall Survival with Momelotinib Vs Best Available Therapy in Patients with Ruxolitinib-Experienced Myelofibrosis: A Matching-Adjusted Indirect Comparison (ASH 2024) - "BAT included hydroxyurea, danazol, corticosteroids, erythropoiesis-stimulating agents, and investigational agents. These results suggest that momelotinib provides a greater OS benefit than BAT in patients with MF previously treated with ruxolitinib, and they complement SIMPLIFY-2 and MOMENTUM results supporting the use of momelotinib as a standard of care in patients with anemia in this setting."

Clinical • Anemia • Hematological Disorders • Infectious Disease • Myelofibrosis • Novel Coronavirus Disease • Oncology • Thrombocytopenia • ACVR1 • JAK1 • JAK2

Real World Efficacy and Safety of Momelotinib for Myelofibrosis: Evaluation of a UK-Wide Study Confirms 40% Anaemia Response Rate in a Non-Clinical Trial Cohort (ASH 2024) - "Conclusion Momelotinib demonstrated significant efficacy in reducing spleen volume, improving anemia, and alleviating symptoms in a substantial proportion of MF patients, including as both a 1st or 2nd line JAKi, with a reasonable safety profile. These real-world results support its use as a viable treatment option for myelofibrosis in routine clinical practice."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Anemia • Bone Marrow Transplantation • CNS Disorders • Dermatology • Fatigue • Hematological Disorders • Infectious Disease • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • Thrombocytosis • ACVR1 • ASXL1 • CALR • DNMT3A • JAK1 • TET2

MODULE 3: Managing MF for Patients with Anemia (ASH 2024) - "This program is supported by educational grants from CTI BioPharma, a Sobi Company, Geron Corporation, GSK, Incyte Corporation and Karyopharm Therapeutics.Rationale for the activity of momelotinib in patients with MF and anemia; differences between momelotinib and other approved JAK inhibitors Key findings from the Phase III MOMENTUM study of momelotinib versus danazol for symptomatic, anemic patients previously treated with a JAK inhibitor Efficacy and safety of momelotinib compared to ruxolitinib in the subset of patients with JAK inhibitor-naïve disease and anemia in the Phase III SIMPLIFY-1 trial FDA approval of momelotinib for patients with MF and disease-related anemia; current role in disease management Comparative tolerability/toxicity profile of momelotinib versus other approved JAK inhibitors Retrospective analysis of the PERSIST-2 study to evaluate the utility of pacritinib for patients with MF and anemia; role, if any, of pacritinib in this setting"

Clinical • Anemia • Hematological Disorders

Spatial-transcriptomic profiling: a new lens for understanding myelofibrosis pathophysiology. (PubMed, Cell Commun Signal) - "Current therapeutic strategies include JAK inhibitors like Ruxolitinib, which target the JAK-STAT pathway, alongside supportive treatments such as blood transfusions, erythropoiesis-stimulating agents and developing combinatorial approaches...Recently approved JAK inhibitors, including Fedratinib, Pacritinib, and Momelotinib, have expanded the therapeutic landscape...These technologies elucidate the role of the spleen in MF, highlighting its transformation into a site of abnormal hematopoietic activity, fibrotic changes, and immune cell infiltration, functioning as a "tumor surrogate." By profiling diverse cell populations and molecular alterations within the BM and spleen, SRT facilitates a deeper understanding of MF pathophysiology, helping identify novel therapeutic targets and biomarkers. Ultimately, integrating spatial transcriptomics into MF research promises to enhance diagnostic precision and therapeutic innovation, addressing the multifaceted..."

Journal • Review • Bone Marrow Transplantation • Fatigue • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Transplantation • CALR • JAK2 • SRSF2 • TET2 • TGFB1 • TNFA • TP53

Considerations before HSCT for Patients with MF (ICBMT 2024) - "High-risk candidates often receive JAK inhibitors like ruxolitinib, with response-based models aiding in timing decisions...Alternatives like fedratinib, pacritinib, and momelotinib show promise, though pre-transplant data is limited...Splenic irradiation remains an option for non-surgical candidates. This lecture aims to provide a comprehensive review of recent data and clinical insights to guide the management of MF patients undergoing HSCT, addressing the complexities of candidate selection, timing, and splenomegaly treatment to optimize patient outcomes."

Clinical • Bone Marrow Transplantation • Fibrosis • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • CALR

Comparative efficacy and hematologic safety of different dosages of JAK inhibitors in the treatment of myelofibrosis: a network meta-analysis. (PubMed, Front Oncol) - "The therapeutic landscape for MF has advanced with the development of Janus kinase inhibitors (JAKis) like ruxolitinib (RUX), fedratinib (FED), pacritinib (PAC), and momelotinib (MMB), aiming to alleviate symptoms and enhance patient comfort. Therefore, there is an urgent need for personalized dosing strategies to optimize the balance between efficacy and safety, with careful consideration of patient-specific factors. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023424179."

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

How I individualize selection of JAK inhibitors for patients with myelofibrosis. (PubMed, Blood) - "Ruxolitinib and fedratinib can cause myelosuppression and are recommended for patients with myeloproliferative MF. Approval of 2 less myelosuppressive JAKi, pacritinib and momelotinib, provided essential treatment options for patients with severe thrombocytopenia and anemia, respectively...Judicious treatment decisions of JAKi can be made with in-depth understanding of the pivotal clinical trials on JAKi and their therapeutic attributes and should be guided by the dominant clinical manifestations and the type/degree of cytopenia(s). This article reviews our clinical approach to treatment with JAKi and their sequencing in MF patients by presenting 3 clinical vignettes."

Journal • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • ACVR1

SOHO State of the Art Updates and Next Questions | Choosing and Properly Using a JAK Inhibitor in Myelofibrosis. (PubMed, Clin Lymphoma Myeloma Leuk) - "Following the initial approval of ruxolitinib in 2011, three additional agents have been approved: fedratinib, pacritinib, and momelotinib. However, with multiple JAK inhibitors now approved, sequencing of these agents appears poised to improve outcomes. Additionally, novel JAK inhibitors and JAK inhibitor-based combinations are in clinical development."

Journal • Review • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Myelofibrosis • Oncology • Thrombocytopenia • Transplantation

Discovery of Janus Kinase and Histone Deacetylase Dual Inhibitors as a New Strategy to Treat Psoriasis. (PubMed, J Med Chem) - "Importantly, compound 11i significantly ameliorated psoriasis-like skin lesions in an imiquimod-induced murine model with low toxicity, which was superior to JAK inhibitor momelotinib, HDAC inhibitor vorinostat, and their combination. This work provided a proof-of-concept for JAK/HDAC dual inhibitors as a promising strategy for the treatment of psoriasis."

Epigenetic controller • Journal • Dermatology • Immunology • Inflammation • Psoriasis • JAK2 • TNFA

Pacritinib and Momelotinib for Treatment Myelofibrosis: A Single Institution Experience on Safety and Tolerability (MPN 2024) - No abstract available

Clinical • Myelofibrosis

Cost Comparison of Ruxolitinib and Momelotinib in Patients With Myelofibrosis and Anemia (MPN 2024) - No abstract available

Clinical • HEOR • Reimbursement • US reimbursement • Anemia • Hematological Disorders • Myelofibrosis

Efficacy and Safety of Momelotinib in Myelofibrosis: A Systematic Review and Meta-Analysis with a Focus on Anemia Outcomes (MPN 2024) - No abstract available

Retrospective data • Review • Anemia • Hematological Disorders • Myelofibrosis

Clinical Outcomes With Momelotinib vs Ruxolitinib in Patients with Myelofibrosis Who Have Moderate Anemia: Subgroup Analysis of SIMPLIFY-1 (MPN 2024) - No abstract available

Clinical • Clinical data • Anemia • Hematological Disorders • Myelofibrosis

Addressing Myelofibrosis in Patients with Anemia: An interactive discussion of OJJAARA (Momelotinib) (MPN 2024) - No abstract available

Clinical • Anemia • Hematological Disorders • Myelofibrosis

HEPATITIS B VIRUS REACTIVATION IN CANCER PATIENTS RECEIVING JANUS KINASE INHIBITORS (AASLD 2024) - " We retrospectively analyzed all consecutive cancer patients with past HBV infection (non-reactive HBV surface antigen [HBsAg], reactive HBV core antibody [anti-HBc]) or chronic HBV infection (reactive HBsAg, reactive anti-HBc) receiving JAKis (ruxolitinib, momelotinib, or tofacitinib) at MD Anderson Cancer Center from April 1, 2015, through May 1, 2024...Of the 28 patients who received an antiviral, 27 (96%) received entecavir. JAKis pose a low to intermediate risk of HBVr in cancer patients with past HBV. On the basis of our preliminary results, patients with past HBV infection should be monitored for HBVr while on JAKis, and antiviral therapy should be started promptly if HBVr occurs."

Clinical • Graft versus Host Disease • Hepatitis B • Hepatology • Immunology • Infectious Disease • Liver Failure • Myelofibrosis • Oncology • Polycythemia Vera