Omvoh

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 …

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions : Serious hypersensitivity reactions, including anaphylaxis and infusion-related reactions, have been reported. If a severe hypersensitivity reaction occurs, discontinue and initiate appropriate treatment. ( 5.1 ) Infections : OMVOH may increase the risk of infection. Do not initiate treatment with OMVOH in patients with a clinically important active infection until the infection resolves or is adequately treated. If a serious infection develops, do not administer OMVOH until the infection resolves. ( 5.2 ) Tuberculosis : Do not administer OMVOH to patients with active TB infection. Monitor patients receiving OMVOH for signs and symptoms of active TB during and after treatment. ( 5.3 ) Hepatotoxicity : Drug-induced liver injury has been reported. Monitor liver enzymes and bilirubin levels at baseline and for at least 24 weeks of treatment and thereafter according to routine patient management. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. ( 5.4 ) Immunizations : Avoid use of live vaccines. ( 5.5 ) 5.1 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis during intravenous infusion, have been reported with OMVOH administration. Infusion-related hypersensitivity reactions, including mucocutaneous erythema and pruritus, were reported during induction [see Adverse Reactions ( 6.1 )] . If a severe hypersensitivity reaction occurs, discontinue OMVOH immediately and initiate appropriate treatment. 5.2 Infections OMVOH may increase the risk of infection [see Adverse Reactions ( 6.1 )] . Do not initiate treatment with OMVOH in patients with a clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing OMVOH. Instruct patients to seek medical advice if signs or symptoms of clinically important acute or chronic infection occur. If a serious infection develops or an infection is not responding to standard therapy, monitor the patient closely and do not administer OMVOH until the infection resolves. 5.3 Tuberculosis Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with OMVOH. Do not administer OMVOH to patients with active TB infection. Initiate treatment of latent TB prior to administering OMVOH. Consider anti-TB therapy prior to initiation of OMVOH in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after OMVOH treatment. In clinical trials, subjects were excluded if they had evidence of active TB, a past history of active TB, or were diagnosed with latent TB at screening. 5.4 Hepatotoxicity A case of drug-induced liver injury (alanine aminotransferase [ALT] 18x the upper limit of normal (ULN), aspartate aminotransferase [AST] 10x ULN, and total bilirubin 2.4x ULN) in conjunction with pruritus was reported in a clinical trial subject following a longer than recommended induction regimen. OMVOH was discontinued. Liver test abnormalities eventually returned to baseline. Evaluate liver enzymes and bilirubin at baseline and for at least 24 weeks of treatment. Monitor thereafter according to routine patient management. Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction. 5.5 Immunizations Avoid use of live vaccines in patients treated with OMVOH. Medications that interact with the immune system may increase the risk of infection …

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 ).

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.

8.1 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.

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…