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Omvoh ™ (mirikizumab-mrkz) injection
300 mg/15 mL, 100 mg/mL
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What is the mechanism of action of Omvoh™ (mirikizumab-mrkz) in inflammatory bowel disease?
Mirikizumab is a humanized monoclonal antibody directed against interleukin-23, a key cytokine in the inflammatory process of IBD.
Inflammatory Bowel Disease
Inflammatory bowel disease including ulcerative colitis (UC) and Crohn's disease (CD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract.1,2
Although the immune response to commensal microbiota is usually self-limiting, in patients with UC or CD, environmental factors and genetic susceptibility can combine with overactivation of the immune response to cause impaired barrier function of the intestinal wall.1-3
This exaggerated immune response causes the release of proinflammatory cytokines leading to additional inflammation.1
Role of Interleukin-23 in Inflammatory Bowel Disease
Interleukin-23 (IL-23), released from activated dendritic cells and macrophages, is a key cytokine in the inflammatory processes of inflammatory bowel disease (IBD), facilitating the release of
- tumor necrosis factor alpha (TNF-alpha)
- interleukin-21 (IL-21), and
- interleukin-17 (IL-17).3
A detailed description of IL-23 and the pathophysiology of IBD can be viewed in this video link.5
Mechanism of Action
Mirikizumab is a humanized immunoglobulin G4-variant monoclonal antibody directed against the p19 subunit of human IL-23. Mirikizumab neutralizes IL-23, preventing it from activating the IL-23 receptor complex.6-9
Mirikizumab does not bind to the p40 subunit, which is shared between IL-23 and interleukin-12 (IL-12), and thus mirikizumab has no effect on IL-12. The mirikizumab/IL-23 complex does not interfere with IL-12 signaling.6-9
Nonclinical data support that specific inhibition of the p19 subunit of IL-23, therefore sparing the IL-12 pathway, preserves the perceived protective role of IL-12 in immune responses during infections and in antitumor immunity.1,10,11
A detailed description of mirikizumab's mechanism of action can be viewed in this video link.12
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14(5):329-342. https://doi.org/10.1038/nri3661
2Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet. 2017;389(10080):1756-1770. https://doi.org/10.1016/S0140-6736(16)32126-2
3Abraham C, Cho JH. IL-23 and autoimmunity: new insights into the pathogenesis of inflammatory bowel disease. Annu Rev Med. 2009;60(1):97-110. https://doi.org/10.1146/annurev.med.60.051407.123757
4Rieder F, Brenmoehl J, Leeb S, et al. Wound healing and fibrosis in intestinal disease. Gut. 2007;56(1):130-139. https://doi.org/10.1136/gut.2006.090456
5Interleukin-23 and the pathophysiology of inflammatory bowel disease. Accessed October 30, 2023. https://www.lillymedical.com/en-us/answers/video-what-is-the-pathophysiology-of-inflammatory-bowel-disease-156474?hcpToken=A12DSa08bhrd123gg8
6Maari C, Bissonnette R, Papp KA, et al. Safety, efficacy, and pharmacokinetics of a p19-directed IL-23 antibody in patients with plaque psoriasis and healthy subjects. Poster presented at: 25th Congress of the European Academy of Dermatology and Venereology; September 28-October 2, 2016; Vienna, Austria.
7Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: what can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis? Ann Rheum Dis. 2018;77(2):175-187. https://doi.org/10.1136/annrheumdis-2017-211555
8Reich K, Rich P, Maari C, et al; AMAF Investigators. Efficacy and safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: results from a randomized phase II study. Br J Dermatol. 2019;181(1):88-95. https://doi.org/10.1111/bjd.17628
9Sandborn WJ, Ferrante M, Bhandari BR, et al. Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with ulcerative colitis. Gastroenterology. 2020;158(3):537-549.e10. https://doi.org/10.1053/j.gastro.2019.08.043
10Hamza T, Barnett JB, Li B. Interleukin 12 a key immunoregulatory cytokine in infection applications. Int J Mol Sci. 2010;11(3):789-806. https://doi.org/10.3390/ijms11030789
11Tugues S, Burkhard SH, Ohs I, et al. New insights into IL-12-mediated tumor suppression. Cell Death Differ. 2015;22(2):237-246. https://doi.org/10.1038/cdd.2014.134
12Mirikizumab mechanism of action. Accessed October 30, 2023. https://www.lillymedical.com/en-us/answers/video-what-is-the-mechanism-of-action-of-mirikizumab-in-inflammatory-bowel-disease-191664?hcpToken=A12DSa08bhrd123gg8
Date of Last Review: April 10, 2023