Omvoh

Indications and Usage ( 1 ) 1/2025 Dosage and Administration Recommended Dosage for Ulcerative Colitis ( 2.2 ) 10/2025 Recommended Dosage for Crohn's Disease ( 2.3 ) 1/2025 Preparation and Administration Instructions for Intravenous Infusion ( 2.4 ) 1/2025 Preparation and Administration Instructions for Subcutaneous Injection( 2.5 ) 10/2025

1 INDICATIONS AND USAGE OMVOH is indicated for the treatment of: moderately to severely active ulcerative colitis in adults. moderately to severely active Crohn's disease in adults. OMVOH TM is an interleukin-23 antagonist indicated for the treatment of: moderately to severely active ulcerative colitis in adults ( 1 ) moderately to severely active Crohn's disease in adults ( 1 )

2 DOSAGE AND ADMINISTRATION Prior to Treatment Initiation Evaluate patients for tuberculosis (TB) infection. ( 2.1 , 5.3 ) Obtain liver enzymes and bilirubin levels. ( 2.1 , 5.4 ) Complete all age-appropriate vaccinations according to current immunization guidelines. ( 2.1 , 5.5 ) Recommended Dosage for Ulcerative Colitis Induction Dosage : Week 0, Week 4, and Week 8: Infuse 300 mg intravenously over at least 30 minutes. ( 2.2 ) Maintenance Dosage : Week 12 and every 4 weeks thereafter: Inject 200 mg subcutaneously (given as either one injection of 200 mg or as two consecutive injections of 100 mg each). ( 2.2 ) Recommended Dosage for Crohn's Disease Induction Dosage : Week 0, Week 4, and Week 8: Infuse 900 mg intravenously over at least 90 minutes. ( 2.3 ) Maintenance Dosage : Week 12 and every 4 weeks thereafter: Inject 300 mg subcutaneously (given as two consecutive injections of 100 mg and 200 mg in any order). ( 2.3 ) Preparation and Administration Instructions See the full prescribing information for preparation, administration and storage information for intravenous infusion and subcutaneous injection. ( 2.2 , 2.3 , 2.4 , 2.5 ) 2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with OMVOH [see Warnings and Precautions ( 5.3 )] . Obtain liver enzymes and bilirubin levels prior to initiating treatment with OMVOH [see Warnings and Precautions ( 5.4 )] . Complete all age-appropriate vaccinations according to current immunization guidelines [see Warnings and Precautions ( 5.5 )] . 2.2 Recommended Dosage for Ulcerative Colitis Induction Dosage Week 0, Week 4, and Week 8: Infuse 300 mg intravenously over at least 30 minutes [see Dosage and Administration ( 2.4 )]. Maintenance Dosage Week 12 and every 4 weeks thereafter : Inject 200 mg subcutaneously (given as one injection of 200 mg or as two consecutive injections of 100 mg each) [see Dosage and Administration ( 2.5 ) and How Supplied/Storage and Handling ( 16 )] . 2.3 Recommended Dosage for Crohn's Disease Induction Dosage Week 0, Week 4, and Week 8 : Infuse 900 mg intravenously over at least 90 minutes [see Dosage and Administration ( 2.4 )]. Maintenance Dosage Week 12 and every 4 weeks thereafter : Inject 300 mg subcutaneously (given as two consecutive injections of 100 mg and 200 mg in any order) [see Dosage and Administration ( 2.5 ) and How Supplied/Storage and Handling ( 16 )] . 2.4 Preparation and Administration Instructions for Intravenous Infusion OMVOH for intravenous use is intended for administration by a healthcare provider using aseptic technique. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be a clear to opalescent, colorless to slightly yellow to slightly brown solution, and free of visible particles. Do not use OMVOH if it is cloudy or there are visible particles. Prior to intravenous administration, determine the dose needed based on the patient's indication (see Table 1 below). For Crohn's disease, discard 45 mL of the infusion bag prior to adding vial contents. Withdraw the required amount of solution from the vial(s) using a 18 gauge to 21 gauge needle and transfer to an infusion bag containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection (see Table 1 below). Do not mix with other drugs. Do not dilute or infuse through the same intravenous line with other solutions. Table 1: Intravenous Induction Dose and Volume of Diluent Required Indication Intravenous Induction Dose Number of OMVOH 300mg/15mL vials needed Volume of 0.9% Sodium Chloride or 5% Dextrose Injection Ulcerative colitis 300 mg 1 50 mL, 100 mL, or 250 mL Crohn's disease 900 mg 3 100 mL or 250 mL Gently invert the infusion bag to mix the contents. Do not shake the prepared infusion bag. Connect the intravenous administration set (infusion line) to …

3 DOSAGE FORMS AND STRENGTHS OMVOH is a clear to opalescent, colorless to slightly yellow to slightly brown solution available as: Intravenous Infusion: Injection: 300 mg/15 mL (20 mg/mL) solution in a single-dose vial Subcutaneous Use: Injection: 100 mg/mL solution in a single-dose prefilled pen Injection: 100 mg/mL solution in a single-dose prefilled syringe Injection: 200 mg/2 mL solution in a single-dose prefilled pen Injection: 200 mg/2 mL (100 mg/mL) solution in a single-dose prefilled syringe Intravenous Infusion ( 3 ) Injection: 300 mg/15 mL (20 mg/mL) solution in a single-dose vial Subcutaneous Injection ( 3 ): Injection: 100 mg/mL solution in a single-dose prefilled pen Injection: 100 mg/mL solution in a single-dose prefilled syringe Injection: 200 mg/2 mL solution in a single-dose prefilled pen Injection: 200 mg/2 mL (100 mg/mL) solution in a single-dose prefilled syringe

4 CONTRAINDICATIONS OMVOH is contraindicated in patients with a history of serious hypersensitivity reaction to mirikizumab-mrkz or any of the excipients [see Warnings and Precautions ( 5.1 )] . History of serious hypersensitivity reaction to mirikizumab-mrkz or any of the excipients. ( 4 , 5.1 ).

6 ADVERSE REACTIONS The following topics are also discussed in detail in the Warnings and Precautions section: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Infections [see Warnings and Precautions ( 5.2 )] Tuberculosis [see Warnings and Precautions ( 5.3 )] Hepatotoxicity [see Warnings and Precautions ( 5.4 )] Most common adverse reactions are: Ulcerative colitis (≥2%) : Induction : upper respiratory tract infections and arthralgia. ( 6.1 ) Maintenance: upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection. ( 6.1 ) Crohn's disease (≥5%) : upper respiratory tract infections, injection site reactions, headache, arthralgia, and elevated liver tests ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Ulcerative Colitis OMVOH was studied up to 12 weeks in subjects with moderately to severely active ulcerative colitis in a randomized, double-blind, placebo-controlled induction study (UC-1). In subjects who responded to induction therapy in UC-1, long term safety up to 52 weeks was evaluated in a randomized, double-blind, placebo-controlled maintenance study (UC-2) and a long-term extension study [see Clinical Studies ( 14.1 )] . In the induction study (UC-1), 1279 subjects were enrolled of whom 958 received OMVOH 300 mg administered as an intravenous infusion at Weeks 0, 4, and 8. In the maintenance study (UC-2), 581 subjects were enrolled of whom 389 received OMVOH 200 mg administered as a subcutaneous injection every 4 weeks. Table 2 summarizes the adverse reactions reported in at least 2% of subjects and at a higher frequency than placebo during UC-1. Table 2: Adverse Reactions a in Subjects with Ulcerative Colitis through Week 12 in a Placebo-Controlled Induction Study (UC-1) a Reported in at least 2% of subjects and at a higher frequency than placebo. b OMVOH 300 mg as an intravenous infusion at Weeks 0, 4, and 8. c Upper respiratory tract infections includes related terms (e.g., COVID-19, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection). Adverse Reactions OMVOH 300 mg Intravenous Infusion b N=958 n (%) Placebo N=321 n (%) Upper respiratory tract infections c 72 (8%) 20 (6%) Arthralgia 20 (2%) 4 (1%) In the induction study (UC-1), infusion-related hypersensitivity reactions were reported by 4 (0.4%) subjects treated with OMVOH and 1 (0.3%) subject treated with placebo. Table 3 summarizes the adverse reactions reported in at least 2% of subjects and at a higher frequency than placebo during the 40-week controlled period of UC-2. Table 3: Adverse Reactions a in Subjects with Ulcerative Colitis through Week 40 In a Placebo-Controlled Maintenance Study (UC-2) a Reported in at least 2% of subjects and at a higher frequency than placebo b OMVOH 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter for up to an additional 40 weeks. c Upper respiratory tract infections includes related terms (e.g., COVID-19, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection). d Injection site reactions includes related terms (e.g., erythema, hypersensitivity, pain, reaction, and urticaria at the injection site). e Rash is composed of several similar terms. f Herpes viral infection includes related terms (e.g., herpes zoster, herpes simplex, and oral herpes). Adverse Reactions OMVOH 200 mg Subcutaneous Injection b N=389 n (%) Placebo N=192 n (%) Upper respiratory tract infections c 53 (14%) 23 (12%) Injection site reactions d 34 (9%) 8 (4%) Arthralgia 26 (7%) 8 (4%) Rash e 16 …

7 DRUG INTERACTIONS 7.1 CYP450 Substrates Increased concentrations of cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation associated with certain diseases including Crohn's disease may suppress the formation of CYP450 enzymes. Therapeutic proteins, including mirikizumab-mrkz, that decrease the concentrations of these pro-inflammatory cytokines may increase the formation of CYP450 enzymes resulting in decreased CYP450 substrate exposure. Upon initiation or discontinuation of OMVOH in patients treated with concomitant CYP450 substrates, monitor drug concentrations or other therapeutic parameters, and adjust the dosage of the CYP450 substrate as needed. See the prescribing information of specific CYP450 substrates.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to OMVOH during pregnancy. Pregnant women exposed to OMVOH and healthcare providers are encouraged to call Eli Lilly and Company at 1-800-Lilly-Rx (1-800-545-5979). Risk Summary Available data from case reports of mirikizumab-mrkz use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Although there are no data on mirikizumab-mrkz, monoclonal antibodies can be actively transported across the placenta, and mirikizumab-mrkz may cause immunosuppression in the in utero-exposed infant. An enhanced pre- and post-natal development study conducted in pregnant monkeys at a dose 20 times the maximum recommended human dose (MRHD) revealed no adverse developmental effects to the developing fetus, or harm to infant monkeys from birth through 6 months of age. There are risks of adverse pregnancy outcomes associated with increased disease activity in women with inflammatory bowel disease (see Clinical Considerations) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and Embryo/Fetal Risk Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. It is unclear whether mirikizumab-mrkz may interfere with an infant's immune response to infections. Therefore, monitoring for the development of serious infection during the first 2 months of life in infants exposed in utero is recommended. Data Animal Data An enhanced pre- and postnatal development study was conducted in cynomolgus monkeys administered mirikizumab-mrkz by intravenous injection during organogenesis to parturition at a dose of 300 mg/kg twice weekly (20 times the MRHD based on exposure comparisons). Mirikizumab-mrkz crossed the placenta in monkeys. No maternal toxicity was noted in this study. No mirikizumab-mrkz-related effects on morphological, functional or immunological development were observed in infant monkeys from birth through 6 months of age. However, incidences of embryo/fetal loss were higher in the treated groups compared to control (6.7% [1 of 15] in controls vs 26.7% [4 of 15] at 300 mg/kg (20 times the MRHD, based on exposure comparisons) but were within the range of historical control data. Following delivery, most adult female cynomolgus monkeys and all infants from the mirikizumab-mrkz-treated group had measurable serum concentrations up to 28 days postpartum. In the infant monkeys, mean serum concentrations were approximately 4.8 times the respective mean maternal concentrations. 8.2 Lactation Risk Summary There are no data on the presence of mirikizumab-mrkz in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous maternal IgG and monoclonal antibodies are transferred in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to mirikizumab-mrkz are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for OMVOH and any potential adverse effe …

12.1 Mechanism of Action Mirikizumab-mrkz is a humanized IgG4 monoclonal antibody that selectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is involved in mucosal inflammation and affects the differentiation, expansion, and survival of T cell subsets, and innate immune cell subsets, which represent sources of pro-inflammatory cytokines. Research in animal models has shown that pharmacologic inhibition of IL-23p19 can ameliorate intestinal inflammation. Mirikizumab-mrkz inhibits the release of pro-inflammatory cytokines and chemokines.

11 DESCRIPTION Mirikizumab-mrkz is a humanized immunoglobulin G4 (IgG4) variant monoclonal antibody that is directed against the p19 subunit of IL-23 and does not bind IL-12. Mirikizumab-mrkz is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology and it is composed of two identical light chain polypeptides and two identical heavy chain polypeptides with an overall molecular weight of approximately 147 kDa. OMVOH for intravenous infusion for ulcerative colitis and Crohn's disease OMVOH (mirikizumab-mrkz) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow to slightly brown solution in a single-dose vial for intravenous infusion after dilution. OMVOH injection 300 mg /15 mL vial is available in 2 formulations: Each mL contains 20 mg of mirikizumab-mrkz, anhydrous citric acid (0.4 mg), polysorbate 80 (0.5 mg), sodium chloride (8.8 mg), sodium citrate (2.1 mg), and Water for Injection. The OMVOH solution has a pH range of 5.0 to 6.0. Each mL contains 20 mg of mirikizumab-mrkz, anhydrous citric acid (0.1 mg), histidine (0.1 mg), L-histidine hydrochloride monohydrate (0.9 mg), mannitol (33 mg), polysorbate 80 (0.5 mg), sodium chloride (2.9 mg), sodium citrate (0.2 mg), and Water for Injection. The OMVOH solution has a pH range of 5.0 to 5.8. OMVOH (mirikizumab-mrkz) injection 100 mg/mL prefilled pen or prefilled syringe for subcutaneous use for ulcerative colitis and Crohn's disease OMVOH (mirikizumab-mrkz) injection is a sterile, preservative free, clear to opalescent, colorless to slightly yellow to slightly brown solution for subcutaneous use available as 100 mg of mirikizumab-mrkz in a 1 mL single-dose prefilled pen or single-dose prefilled syringe. The prefilled pen and prefilled syringe contain a 1 mL glass syringe with a fixed 27-gauge 1⁄2 inch needle. The OMVOH 100 mg prefilled pen and prefilled syringe are manufactured to deliver 100 mg of mirikizumab-mrkz. Each mL is composed of 100 mg mirikizumab-mrkz, histidine (0.1 mg), L-histidine hydrochloride monohydrate (0.9 mg), mannitol (33 mg), polysorbate 80 (0.3 mg), sodium chloride (2.9 mg), and Water for Injection. The OMVOH solution has a pH range of 5.0 to 5.8. OMVOH (mirikizumab-mrkz) injection 200 mg/2 mL prefilled pen or 200 mg/2 mL (100 mg/mL) prefilled syringe for subcutaneous use for ulcerative colitis and Crohn's disease OMVOH (mirikizumab-mrkz) injection is a sterile, preservative free, clear to opalescent, colorless to slightly yellow to slightly brown solution for subcutaneous use. The 2 mL prefilled pen and prefilled syringe each contain a 2 mL glass syringe with a fixed 27-gauge 8 mm needle. The OMVOH 200 mg prefilled pen and prefilled syringe are manufactured to deliver 200 mg of mirikizumab-mrkz. Each mL is composed of 100 mg mirikizumab-mrkz, histidine (0.1 mg), L-histidine hydrochloride monohydrate (0.9 mg), mannitol (33 mg), polysorbate 80 (0.3 mg), sodium chloride (2.9 mg), and Water for Injection. The OMVOH solution has a pH range of 5.0 to 5.8.

16 HOW SUPPLIED/STORAGE AND HANDLING OMVOH (mirikizumab-mrkz) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow to slightly brown solution for intravenous infusion or subcutaneous injection. OMVOH is supplied in indication specific packaging as: Table 10: Packaging Information for OMVOH Presentation Indication Package Size NDC Code Single-dose Vial 300 mg/15 mL (20 mg/mL) Ulcerative colitis and Crohn's disease Carton of 1 0002-7575-01 Single-dose Prefilled Pen 100 mg/mL + 100 mg/mL Ulcerative colitis Carton of 2 0002-8011-27 200 mg/2 mL Ulcerative colitis Carton of 1 0002-3116-11 200 mg/2 mL + 100 mg/mL Crohn's disease Carton of 2 (1 of each) 0002-7717-11 Single-dose Prefilled Syringe 100 mg/mL + 100 mg/mL Ulcerative colitis Carton of 2 0002-8870-27 200 mg/2 mL (100 mg/mL) Ulcerative colitis Carton of 1 0002-1442-11 200 mg/2 mL (100 mg/mL) + 100 mg/mL Crohn's disease Carton of 2 (1 of each) 0002-7722-11 Note to Pharmacist: The entire carton of 2 prefilled pen or 2 prefilled syringes are to be dispensed as a unit. Each 100 mg/mL single-dose prefilled pen or prefilled syringe consists of a 1 mL glass syringe with a fixed 27-gauge 1⁄2 inch needle. Each 200 mg/2 mL single-dose prefilled pen or 200 mg/2 mL (100 mg/mL) prefilled syringe consists of a 2 mL glass syringe with a fixed 27-gauge 8 mm needle. Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not use OMVOH if it has been frozen. Do not shake. Keep OMVOH in the original carton to protect from light until the time of use. OMVOH is sterile and preservative-free. Discard any unused portion. If needed, the prefilled pen or prefilled syringe may be stored at room temperature up to 30°C (86°F) for up to 2 weeks in the original carton to protect from light. Once OMVOH has been stored at room temperature, do not return to the refrigerator. If these conditions are exceeded, OMVOH must be discarded. The vial, prefilled pen, and prefilled syringe are not made with dry natural rubber latex.