* Omjjara approved for use in both newly diagnosed or previously treated myelofibrosis patients
* Differentiated mechanism of action addresses key manifestations of myelofibrosis, namely anaemia, constitutional symptoms and splenomegaly
* In
This is the fourth major regulatory approval for GSK's momelotinib in the treatment of myelofibrosis, following approval under the brand name Ojjaara from the
Myelofibrosis is a blood cancer that affects approximately 1 in 500,000 people worldwide, with up to 5,000 patients impacted in Japan.4,5,6 In
The approval is based on data from the MOMENTUM and SIMPLIFY-1 pivotal phase III trials. MOMENTUM was designed to evaluate the safety and efficacy of momelotinib versus danazol for the treatment and reduction of key manifestations of myelofibrosis in an anaemic, symptomatic, JAK inhibitor-experienced population. SIMPLIFY-1 was designed to evaluate the efficacy and safety of momelotinib versus ruxolitinib in myelofibrosis patients who had not received a prior JAK inhibitor therapy. About Omjjara (momelotinib)
Momelotinib has a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor, type I (ACVR1).1,21,22,23 Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly.1,21,23 Additionally, inhibition of ACVR1 leads to a decrease in circulating hepcidin levels, potentially contributing to anaemia-related benefit.1,21,22,23
In
In
Please refer to the updated Product Information (PI) for precautions concerning indication and important dosage, administration, and safety information in
Myelofibrosis is a rare blood cancer that disrupts the body's normal production of blood cells because of dysregulated JAK-signal transducer and activator of transcription protein signalling. The clinical hallmarks of myelofibrosis are splenomegaly (enlarged spleen), severely low blood counts, including anaemia and thrombocytopenia, and debilitating constitutional symptoms, such as fatigue, night sweats and bone pain, attributable to ineffective haematopoiesis and excessive production of proinflammatory cytokines.28,29 About the pivotal clinical trials
MOMENTUM was a phase III, global, multicentre, randomised, double-blind study investigating momelotinib versus danazol in patients (n=195) with myelofibrosis who were symptomatic and anaemic and had been previously treated with a licensed JAK inhibitor. The trial was designed to evaluate the safety and efficacy of momelotinib for treating and reducing key hallmarks of the disease: symptoms, blood transfusions (due to anaemia) and splenomegaly. The MOMENTUM trial met all its primary and key secondary endpoints, demonstrating statistically significant response with respect to constitutional symptoms, splenic reduction and transfusion independence in patients treated with momelotinib versus danazol (Total Symptom Score reduction of 50% or greater: 25% momelotinib, 9% danazol, p=0.0095; reduction of spleen volume by 35% or greater: momelotinib 22%, danazol 3%, p=0.0011; no transfusions and all haemoglobin values >=8 g/dL in the 12 weeks prior to week 24: momelotinib 30%, danazol 20%).30 The most common non-haematological treatment-emergent adverse events in momelotinib-treated patients over the entire study period as of the data cutoff were diarrhoea (45 [26%] of 171) and asthenia (28 [16%]); the most common grades 3 and 4 treatment-emergent adverse events were thrombocytopenia (33 [19%]) and anaemia (19 [11%]).31 Results from the 24-week randomised treatment period were presented at the 2022
SIMPLIFY-1 was a multicentre randomised, double-blind, phase III study that compared the safety and efficacy of momelotinib to ruxolitinib in patients with myelofibrosis who had not received prior treatment with a JAK inhibitor (momelotinib: n=215 and ruxolitinib: n=217). SIMPLIFY-1 met its primary endpoint, demonstrating non-inferiority of momelotinib to ruxolitinib in spleen volume response (reduction by 35% or greater) with a difference of 9% (95% CI 2%-16%), and substantial improvements in transfusion independence rates (66.5% for momelotinib compared to 49.3% for ruxolitinib), a difference of 18% (95% CI 9%-26%).35,36 The most common grade 3 or higher haematologic abnormalities in either group were thrombocytopenia and anaemia. Grade 3 or higher infections occurred in 7% of patients who received momelotinib and 3% of patients who received ruxolitinib.37 GSK in oncology
GSK is committed to maximising patient survival through transformational medicines, with a current focus on breakthroughs in immuno-oncology and tumour-cell targeting therapies, and development in haematologic malignancies, gynaecologic cancers, and other solid tumours. About GSK
GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D "Risk factors" in GSK's Annual Report on Form 20-F for 2023, and GSK's Q1 Results for 2024. References
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2 Shide K et al. Nationwide prospective survey of secondary myelofibrosis in
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5 Takenaka K et al., Clinical features and outcomes of patients with primary myelofibrosis in
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7 Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: the mayo clinic experience.
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10 Bassiony S, Harrison CN, McLornan DP. Evaluating the Safety, Efficacy, and Therapeutic Potential of Momelotinib in the Treatment of Intermediate/High-Risk Myelofibrosis: Evidence to Date.
11 Kuykendall AT, Shah S, Talati C, et al. Between a rux and a hard place: evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib discontinuation. Ann Hematol. 2018;97(3):435-441.
12 Naymagon, L., Mascarenhas, J. Myelofibrosis-Related Anemia: Current and Emerging Therapeutic Strategies. HemaSphere. 2017;1(1):e1. doi: 10.1097/HS9.0000000000000001
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14 Nicolosi M, et al. Sex and degree of severity influence the prognostic impact of anemia in primary myelofibrosis: analysis based on 1109 consecutive patients. Leukemia. 2018;32(5):1254-1258. https://doi.org/10.1038/s41375-018-0028-x1
15 Tefferi A, et al. Use of the Functional Assessment of Cancer Therapy--anemia in persons with myeloproliferative neoplasm-associated myelofibrosis and anemia.
16 Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021;96(1):145-162. https://doi.org/10.1002/ajh.26050
17 Rumi E, et al. The Genetic Basis of Primary Myelofibrosis and Its Clinical Relevance. Int J Mol Sci. 2020;21(23):8885. https://doi.org/10.3390/ijms21238885
18 QxMD. DIPSS prognosis in myelofibrosis. Accessed
19 QxMD. DIPSS plus score for prognosis of myelofibrosis. Accessed
20 Elena C, et al. Red blood cell transfusion-dependency implies a poor survival in primary myelofibrosis irrespective of IPSS and DIPSS. Haematologica. 2011;96(1):167-170. https://doi.org/10.3324/haematol.2010.031831.
21 Verstovsek S, et al. MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic. Future Oncol. 2021;17(12):1449-1458.
22 Asshoff M, et al. Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood. 2017;129(13):1823-1830.
23 Oh S, et al. ACVR1/JAK1/JAK2 inhibitor momelotinib reverses transfusion dependency and suppresses hepcidin in myelofibrosis phase 2 trial. Blood Adv. 2020;4(18):4282-4291.
24 GSK press release issued
25 GSK press release issued
26 MHRA press release issued
27
28 Atallah E, Verstovsek S. Emerging drugs for myelofibrosis. Expert Opin Emerg Drugs. 2012 Dec;17(4):555-70. doi: 10.1517/14728214.2012.748748. PMID: 23186315; PMCID: PMC5009610.
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30 Verstovsek S, et al. MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic. Future Oncol. 2021;17(12):1449-1458.
31 Gerds AT, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis previously treated with a JAK inhibitor (MOMENTUM): an updated analysis of an international, double-blind, randomised phase 3 study. The Lancet Haematology. 2023;10(9):E735-E746. https://doi.org/10.1016/S2352-3026(23)00174-6.
32 Verstovsek S, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study.
33 Mesa R, et al. Presented at:
34 Gerds AT, et al. Presented at:
35 Mesa R, et al. Presented at: ISPOR 2021.
36 Mesa R, et al. Presented at: SOHO 2021. Poster MPN-303.
37 Mesa RA, Kiladjian JJ, Catalano JV, Devos T, Egyed M, Hellmann A, McLornan D, Shimoda K, Winton EF, Deng W, Dubowy RL, Maltzman JD, Cervantes F, Gotlib J. SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor-Naïve Patients With Myelofibrosis. J Clin Oncol. 2017
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