Ojjaara (momelotinib) / GSK - LARVOL DELTA

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

ENGINEERING CAR-T CELLS FOR EFFECTIVE THERAPY AMID JAK INHIBITION (EBMT 2025) - "Expansion and receptiveness to retroviral transduction of T-Cells isolated from patients taking oral JAK1/2 inhibitors ruxolitinib (Rux), momelotinib (Mom) as well as myelofibrosis patients not on JAKi therapy were compared to healthy donors. Further exploration of JAK inhibition was performed with titrations of Rux, Mom and the JAK2-selective inhibitor fedratinib (Fed), either by pre-treating CAR-T cells with the inhibitor or spiking it directly into the assays... Overall, the data indicate that functioning CAR-T products can be successfully manufactured from JAKi patient material. However, post-manufacture, JAKi was found to impede the efficacy of CAR-T when co-treated, particularly over periods of long-term exposure. 'On/off' regiments of low dose JAKi may warrant further exploration if used as co-therapy."

CAR T-Cell Therapy • IO biomarker • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Oncology • CALR • CD34

ENGINEERING CAR-T CELLS FOR EFFECTIVE THERAPY AMID JAK INHIBITION (EBMT 2025) - "Expansion and receptiveness to retroviral transduction of T-Cells isolated from patients taking oral JAK1/2 inhibitors ruxolitinib (Rux), momelotinib (Mom) as well as myelofibrosis patients not on JAKi therapy were compared to healthy donors. Further exploration of JAK inhibition was performed with titrations of Rux, Mom and the JAK2-selective inhibitor fedratinib (Fed), either by pre-treating CAR-T cells with the inhibitor or spiking it directly into the assays... Overall, the data indicate that functioning CAR-T products can be successfully manufactured from JAKi patient material. However, post-manufacture, JAKi was found to impede the efficacy of CAR-T when co-treated, particularly over periods of long-term exposure. 'On/off' regiments of low dose JAKi may warrant further exploration if used as co-therapy."

CAR T-Cell Therapy • IO biomarker • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Oncology • CALR • CD34

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

LOW-DOSE SPLENIC IRRADIATION AS PART OF THE CONDITIONING THERAPY PRIOR TO ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR MYELOFIBROSIS WITH SPLENOMEGALY (EBMT 2025) - "Four patients had previously been exposed to a single JAK inhibitor (ruxolitinib), and 5 patients had been exposed to two JAK inhibitors (ruxolitinib and either fedratinib or momelotinib). All patients received a reduced intensity conditioning and a GvHD prophylaxis with a calcineurin inhibitor, mycophenolate mofetil, and anti-T-lymphocyte globulin... Low-dose pretransplant splenic irradiation in myelofibrosis showed a significant and rapid reduction of spleen size in all patients with excellent engraftment rates. Spleen size reduction under irradiation predicted further spleen size reduction until engraftment."

Acute Graft versus Host Disease • Graft versus Host Disease • Hepatology • Immunology • Myelofibrosis • Transplantation

GSK brings Melbourne discovered treatment 'home' to Australian patients (BiotechDispatch) - "GSK's OMJJARA (momelotinib) is listed on the PBS from today for people with a form of myelofibrosis....The listing is for treating intermediate or high-risk primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis in patients with moderate to severe anaemia and who are Janus kinase (JAK) inhibitor naïve or have been treated with ruxolitinib."

Reimbursement • Anemia • Myelofibrosis

Immune Checkpoint Protein CD40 and Integrin α5β1 in HCC: Mechanisms Supporting Tumor Survival and Therapy Potential (APASL 2025) - "Treatment with the JAK1 inhibitor CYT387 (2–16 µM) and the ERK1/2 inhibitor U0126 (5–80 µM) reduced CD40 expression in HLFs under IFN-γ stimulation... These findings indicate that CD40 on HCC cells interacts with CD40L on activated CD4+ T cells, preventing apoptosis via the Integrin α5β1–CD40L axis and promoting cancer cell survival. This study highlights the critical role of the CD40–CD40L interaction in HCC progression, suggesting that this pathway may be a promising therapeutic target for poorly differentiated HCC. Table and Figure:Figure 1.Interplay between CD40 and CD40L in HCC"

IO biomarker • Hepatitis C • Hepatocellular Cancer • Hepatology • Oncology • CD27 • CD40 • CD40LG • IFNG

ODYSSEY: Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis (clinicaltrials.gov) - P1/2 | N=56 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting | Phase classification: P2 ➔ P1/2

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

MSD’s Welireg fails reimbursement review again, while Ledaga Gel and Omjjara secure insurance coverage (Korea Biomedical Review) - "MSD's rare disease drug Welireg (belzutifan) has failed to secure reimbursement in its second attempt....Welireg, Ledaga Gel (chlormethine), and Omjjara (momelotinib) were evaluated for new reimbursement. While Ledaga Gel and Omjjara successfully established reimbursement standards, Welireg failed to pass....Welireg is an oral HIF-2α inhibitor indicated for treating renal cell carcinoma, central nervous system hemangioblastoma, and pancreatic neuroendocrine tumors in adult patients with von Hippel-Lindau (VHL) disease who do not require immediate surgery....In October 2024, Synex received approval from the Ministry of Food and Drug Safety for Ledaga Gel as a topical treatment for adult patients with early-stage mycosis fungoides cutaneous T-cell lymphoma (MF-Type CTCL) who had previously undergone skin-directed therapy....GSK’s Omjjara...approved in September 2024 for treating intermediate- or high-risk myelofibrosis."

Reimbursement • Cutaneous T-cell Lymphoma • Hemangioblastoma • Myelofibrosis • Neuroendocrine Neoplasm • Pancreatic Cancer • Renal Cell Carcinoma • Von Hippel-Lindau Syndrome

GSK's Omjjara (momelotinib) approved in Singapore as the first treatment indicated for myelofibrosis patients with anaemia (PRNewswire) - "GSK Singapore today announced that Omjjara (momelotinib) has been locally approved for treatment of disease-related splenomegaly or symptoms in adult patients with moderate to severe anaemia who have primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis and who are Janus Kinase (JAK) inhibitor naive or have been treated with ruxolitinib....GSK's submission for the approval of Omjjara was supported by data from the pivotal MOMENTUM study and a subpopulation of adult patients with anaemia from the SIMPLIFY-1 phase III trial."

Approval • Myelofibrosis

Pharmacological aspects of FDA-approved novel drug therapies against cancer in 2023: a comprehensive review. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "About 29% (16 out of 55) of these newly FAD-approved drugs have been prescribed for various cancers such as locally progressed or metastatic breast cancer, relapsed or refractory multiple myeloma, prostate cancer, non-Hodgkin lymphoma, acute myeloid leukemia, and nasopharyngeal carcinoma. This manuscript covering pharmacological aspects such as therapeutic effects, approved dose, mechanisms of action, pharmacokinetics, adverse effects, contraindications, and safety in special cases like pregnant, lactating, pediatric, and geriatric patients of FDA-approved anticancer drugs shall be of immense importance for researchers, academician, oncologists, and cancer patients."

FDA event • Journal • Review • Acute Myelogenous Leukemia • Breast Cancer • Genito-urinary Cancer • Geriatric Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Prostate Cancer • Solid Tumor

GSK Korea launches myelofibrosis treatment Ojjaara (Korea Biomedical Review) - "GlaxoSmithKline Korea (GSK Korea) has officially launched Ojjaara (ingredient: momelotinib dihydrochloride hydrate), its new treatment for myelofibrosis. The company expects that Ojjaara will address the significant unmet medical need for anemia management while also improving systemic symptoms and splenomegaly, key therapeutic targets in myelofibrosis treatment."

Launch non-US • Myelofibrosis

Targeted Therapies in Myelofibrosis: Present Landscape, Ongoing Studies, and Future Perspectives. (PubMed, Am J Hematol) - "The discovery of the JAK2 V617F mutation prompted the development of JAK inhibitors (JAKi) including the first-in-class JAK1/JAK2 inhibitor ruxolitinib and subsequent approval of fedratinib, pacritinib, and momelotinib. Selective JAK2 V617F inhibitors and targeting of mutant CALR by immunotherapy are the most intriguing and promising approaches. This review focuses on approved and experimental treatments for MF, highlighting their biological background."

IO biomarker • Journal • Review • Bone Marrow Transplantation • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Transplantation • ACVR1 • CALR

Emerging Pathogenetic Mechanisms and New Drugs for Anemia in Myelofibrosis and Myelodysplastic Syndromes. (PubMed, Am J Hematol) - "These include TGF-β ligand traps (luspatercept, elritercept), activin A receptor type 1 (ACVR1)/activin receptor-like kinase 2 (ALK2) inhibitors (momelotinib, zilurgisertib), and anti-hemojuvelin antibody-based therapies (DISC-0974). Luspatercept and momelotinib are approved for anemia related to lower-risk MDS and MF, respectively, and represent an important addition to the treatment armamentarium, along with imetelstat, a telomerase inhibitor, recently ratified for anemia in lower-risk MDS. A promising strategy to overcome the limitations of existing anemia-directed therapies includes the use of drug combinations with complementary mechanisms (luspatercept + erythropoiesis stimulating agents, luspatercept + momelotinib, DISC-0974 + momelotinib), and harnessing the erythropoietic potential of sodium-glucose co-transporter-2 inhibitors (SGLT-2I). Future research should address the complex pathophysiology of anemia, standardize definitions for anemia with gender-specified..."

Journal • Review • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • SMAD2 • SMAD4 • TGFB1

Hemoglobin improvement and patient-reported outcomes in anemic patients with myelofibrosis in momelotinib phase 3 trials (JSMO 2025) - No abstract available

Clinical • P3 data • Patient reported outcomes • Myelofibrosis • Oncology

A Study of Momelotinib in Participants With Low-risk Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Canada’s Drug Agency recommends OJJAARA for public reimbursement (GSK Press Release) - "Ojjaara (momelotinib) has received a reimburse with conditions recommendation from Canada’s Drug Agency (CDA-AMC)....CDA-AMC is recommending that Ojjaara be reimbursed, with conditions, 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."

Reimbursement • Myelofibrosis

“Users of the Drug Registries subjected to Monitoring are hereby informed that…under the SSN reimbursement regime…Omjjara is indicated for the treatment of splenomegaly…with moderate to severe anemia who have primary myelofibrosis, post polycythemia vera myelofibrosis, or post essential thrombocythemia myelofibrosis and who are JAK-naïve or ruxolitinib-experienced.” [Google translation] (Italian Medicines Agency)

Reimbursement • Hematological Malignancies • Myelofibrosis • Oncology

Orphan Drug Designations and Approvals (FDA) - Generic Name: momelotinib, Trade Name: Ojjaara, Date Designated: 08/05/2010, Orphan Designation: Treatment of myelofibrosis, Orphan Designation Status: Designated/Approved.

Orphan drug • Myelofibrosis

EU/3/11/887 - orphan designation for treatment of post-essential thrombocythaemia myelofibrosis (European Medicines Agency) - "On 5 August 2011, orphan designation (EU/3/11/887) was granted by the European Commission to Cres Pharmaceuticals Limited, United Kingdom, for N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt for the treatment of post-essential thrombocythaemia myelofibrosis."

Orphan drug • Myelofibrosis

Evaluation of the Effect of Momelotinib on Cardiac Repolarization: A Thorough QT Study. (PubMed, Clin Pharmacol Drug Dev) - "QTc was evaluated for momelotinib 200 mg (therapeutic dose), momelotinib 800 mg (supratherapeutic dose), moxifloxacin 400 mg (positive control), and placebo. There were no deaths, serious AEs, or AEs leading to study discontinuation. Neither therapeutic nor supratherapeutic doses of momelotinib led to clinically significant effects on the QTc interval, supporting a negative finding for QTc prolongation from this thorough QT study."

Journal

Interferon Inhibitors Increase rAAV Production in HEK293 Cells. (PubMed, J Biotechnol) - "The positive candidates were BX795 (a TBK inhibitor), TPCA-1 (an IKK2 inhibitor), Cyt387 (a JAK1 inhibitor), and ruxolitinib (another JAK1 inhibitor). These candidates were identified using deep well screening, and reproducible titer improvement was achieved in a 30mL shake flask scale. Additionally, genome titer improvement is feasible and scalable in two different media, but the extent of improvement may vary."

Journal • Gene Therapies