Difference between revisions of "Momelotinib (Ojjaara)"
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==Mechanism of action== | ==Mechanism of action== | ||
| − | JAK1/2 | + | From the [https://www.cancer.gov/publications/dictionaries/cancer-drug/def/momelotinib NCI Drug Dictionary]: An orally bioavailable small-molecule inhibitor of Janus kinases 1 and 2 (JAK1/2) with potential antineoplastic activity. Momelotinib competes with JAK1/2 for ATP binding, which may result in inhibition of JAK1/2 activation, inhibition of the JAK-STAT signaling pathway, and so the induction of apoptosis and a reduction of tumor cell proliferation in JAK1/2-expressing tumor cells. |
| + | |||
| + | *[https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7791 IUPHAR/BPS] | ||
==Preliminary data== | ==Preliminary data== | ||
===[[Myelofibrosis]]=== | ===[[Myelofibrosis]]=== | ||
| − | # Pardanani A, Laborde RR, Lasho TL, Finke C, Begna K, Al-Kali A, Hogan WJ, Litzow MR, Leontovich A, Kowalski M, Tefferi A. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia. 2013 Jun;27(6):1322-7. Epub 2013 Mar 5. [https://www.ncbi.nlm.nih.gov/pubmed/23459451 PubMed] | + | # '''CCL09101:''' Pardanani A, Laborde RR, Lasho TL, Finke C, Begna K, Al-Kali A, Hogan WJ, Litzow MR, Leontovich A, Kowalski M, Tefferi A. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia. 2013 Jun;27(6):1322-7. Epub 2013 Mar 5. [https://doi.org/10.1038/leu.2013.71 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3677140/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23459451/ PubMed] [https://clinicaltrials.gov/study/NCT00935987 NCT00935987] |
| − | # '''SIMPLIFY-1:''' 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 Dec 1;35(34):3844-3850. Epub 2017 Sep 20. [ | + | # '''SIMPLIFY-1:''' 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 Dec 1;35(34):3844-3850. Epub 2017 Sep 20. [https://doi.org/10.1200/JCO.2017.73.4418 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6553796/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28930494/ PubMed] [https://clinicaltrials.gov/study/NCT01969838 NCT01969838] |
| + | # '''SIMPLIFY 2:''' Harrison CN, Vannucchi AM, Platzbecker U, Cervantes F, Gupta V, Lavie D, Passamonti F, Winton EF, Dong H, Kawashima J, Maltzman JD, Kiladjian JJ, Verstovsek S. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018 Feb;5(2):e73-e81. Epub 2017 Dec 20. [https://doi.org/10.1016/S2352-3026(17)30237-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29275119/ PubMed] [https://clinicaltrials.gov/study/NCT02101268 NCT02101268] | ||
| + | # '''MOMENTUM:''' Verstovsek S, Gerds AT, Vannucchi AM, Al-Ali HK, Lavie D, Kuykendall AT, Grosicki S, Iurlo A, Goh YT, Lazaroiu MC, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Granacher N, Lee SE, Ocroteala L, Passamonti F, Harrison CN, Klencke BJ, Ro S, Donahue R, Kawashima J, Mesa R; MOMENTUM Study Investigators. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023 Jan 28;401(10373):269-280. [https://doi.org/10.1016/s0140-6736(22)02036-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36709073/ PubMed] [https://clinicaltrials.gov/study/NCT04173494 NCT04173494] | ||
| + | ##'''Update:''' Gerds AT, Verstovsek S, Vannucchi AM, Al-Ali HK, Lavie D, Kuykendall AT, Grosicki S, Iurlo A, Goh YT, Lazaroiu MC, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Granacher N, Lee SE, Ocroteala L, Passamonti F, Harrison CN, Oh S, Klencke BJ, Yu J, Donahue R, Kawashima J, Mesa R. 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. Lancet Haematol. 2023 Sep;10(9):e735-e746. Epub 2023 Jul 27. [https://doi.org/10.1016/s2352-3026(23)00174-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37517413/ PubMed] | ||
| + | |||
| + | ==History of changes in FDA indication== | ||
| + | *2023-09-15: Approved for the treatment of intermediate or high-risk [[Myelofibrosis|myelofibrosis (MF)]], including primary MF or secondary MF [postpolycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia. ''(Based on MOMENTUM & SIMPLIFY-1)'' | ||
| + | |||
| + | ==History of changes in EMA indication== | ||
| + | *2024-01-24: Initial authorization as Omjjara. Omjjara is indicated for the 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. ''(Based on MOMENTUM & SIMPLIFY-1)'' | ||
| + | |||
| + | ==Also known as== | ||
| + | *'''Code names:''' CYT-387, GS-0387 | ||
| + | *'''Brand name:''' Ojjaara, Omjjara | ||
| − | [[Category: | + | [[Category:Drugs]] |
[[Category:Oral medications]] | [[Category:Oral medications]] | ||
| − | [[Category: | + | [[Category:ACVR1 inhibitors]] |
| − | [[Category: | + | [[Category:JAK1 inhibitors]] |
| + | [[Category:JAK2 inhibitors]] | ||
| + | [[Category:JAK3 inhibitors]] | ||
| + | [[Category:TYK2 inhibitors]] | ||
[[Category:Myelofibrosis medications]] | [[Category:Myelofibrosis medications]] | ||
| − | [[Category: | + | [[Category:FDA approved in 2023]] |
| + | [[Category:EMA approved in 2024]] | ||
Latest revision as of 12:21, 23 June 2024
Mechanism of action
From the NCI Drug Dictionary: An orally bioavailable small-molecule inhibitor of Janus kinases 1 and 2 (JAK1/2) with potential antineoplastic activity. Momelotinib competes with JAK1/2 for ATP binding, which may result in inhibition of JAK1/2 activation, inhibition of the JAK-STAT signaling pathway, and so the induction of apoptosis and a reduction of tumor cell proliferation in JAK1/2-expressing tumor cells.
Preliminary data
Myelofibrosis
- CCL09101: Pardanani A, Laborde RR, Lasho TL, Finke C, Begna K, Al-Kali A, Hogan WJ, Litzow MR, Leontovich A, Kowalski M, Tefferi A. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia. 2013 Jun;27(6):1322-7. Epub 2013 Mar 5. link to original article link to PMC article PubMed NCT00935987
- SIMPLIFY-1: 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 Dec 1;35(34):3844-3850. Epub 2017 Sep 20. link to original article link to PMC article PubMed NCT01969838
- SIMPLIFY 2: Harrison CN, Vannucchi AM, Platzbecker U, Cervantes F, Gupta V, Lavie D, Passamonti F, Winton EF, Dong H, Kawashima J, Maltzman JD, Kiladjian JJ, Verstovsek S. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018 Feb;5(2):e73-e81. Epub 2017 Dec 20. link to original article PubMed NCT02101268
- MOMENTUM: Verstovsek S, Gerds AT, Vannucchi AM, Al-Ali HK, Lavie D, Kuykendall AT, Grosicki S, Iurlo A, Goh YT, Lazaroiu MC, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Granacher N, Lee SE, Ocroteala L, Passamonti F, Harrison CN, Klencke BJ, Ro S, Donahue R, Kawashima J, Mesa R; MOMENTUM Study Investigators. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023 Jan 28;401(10373):269-280. link to original article PubMed NCT04173494
- Update: Gerds AT, Verstovsek S, Vannucchi AM, Al-Ali HK, Lavie D, Kuykendall AT, Grosicki S, Iurlo A, Goh YT, Lazaroiu MC, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Granacher N, Lee SE, Ocroteala L, Passamonti F, Harrison CN, Oh S, Klencke BJ, Yu J, Donahue R, Kawashima J, Mesa R. 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. Lancet Haematol. 2023 Sep;10(9):e735-e746. Epub 2023 Jul 27. link to original article PubMed
History of changes in FDA indication
- 2023-09-15: Approved for the treatment of intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF [postpolycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia. (Based on MOMENTUM & SIMPLIFY-1)
History of changes in EMA indication
- 2024-01-24: Initial authorization as Omjjara. Omjjara is indicated for the 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. (Based on MOMENTUM & SIMPLIFY-1)
Also known as
- Code names: CYT-387, GS-0387
- Brand name: Ojjaara, Omjjara