Omvoh Injection, Solution
FDA Label NDC 0002-8011

OMVOH is indicated for the treatment of moderately to severely active ulcerative colitis in adults.

Induction Dosage

The recommended induction dosage of OMVOH is 300 mg administered by intravenous infusion over at least 30 minutes at Week 0, Week 4, and Week 8 [see Dosage and Administration (2.3)].

Maintenance Dosage

The recommended maintenance dosage of OMVOH is 200 mg administered by subcutaneous injection (given as two consecutive injections of 100 mg each) at Week 12, and every 4 weeks thereafter [see Dosage and Administration (2.4)].

Hepatic Enzyme Elevations

In UC-1 through Week 12, alanine aminotransferase (ALT) ≥5X ULN was reported by 1 (0.1%) subject treated with OMVOH 300 mg and 1 (0.3%) subject treated with placebo. Aspartate aminotransferase (AST) ≥5X ULN was reported by 2 (0.2%) subjects treated with OMVOH 300 mg and no subject treated with placebo. These elevations have been noted with and without concomitant elevations in total bilirubin.

In UC-2 through Week 40 (a total of 52 weeks of treatment), 3 (0.8%) subjects treated with OMVOH 200 mg reported ALT ≥5X ULN and 3 (0.8%) subjects reported AST ≥5X ULN; with or without concomitant elevations in total bilirubin. No subjects treated with placebo experienced similar elevations [see Warnings and Precautions (5.4)].

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 69 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. Because mirikizumab-mrkz may interfere with immune response to infections, risks and benefits should be considered prior to administering live vaccines to infants exposed to OMVOH in utero. There are no data regarding infant serum levels of mirikizumab-mrkz at birth and the duration of persistence of mirikizumab-mrkz in infant serum after birth. Although a specific timeframe to delay live virus immunizations in infants exposed in utero is unknown, a minimum of 2 months after birth should be considered because of the half-life of the product.

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 (69 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 (69 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.

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 effects on the breastfed infant from OMVOH or from the underlying maternal condition.

OMVOH for Intravenous Infusion

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. 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 - 6.0.

OMVOH for Subcutaneous Injection

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. The prefilled pen contains a 1 mL glass syringe with a fixed 27-gauge ½ inch needle. The OMVOH 100 mg prefilled pen is manufactured to deliver 100 mg of mirikizumab-mrkz. Each mL is composed of mirikizumab-mrkz (100 mg), anhydrous citric acid (0.4 mg), polysorbate 80 (0.3 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.

Absorption

Following subcutaneous dosing of OMVOH, median (range) T_max was 5 (3.08 to 6.75) days post dose and geometric mean (CV%) absolute bioavailability was 44% (34%).

Injection site location (abdomen, upper arm, or thigh) did not significantly influence bioavailability of mirikizumab-mrkz following subcutaneous injection.

Distribution

The geometric mean (CV%) total volume of distribution in subjects with ulcerative colitis was 4.83 L (21%).

Metabolism/Elimination

Mirikizumab-mrkz is a humanized IgG4 monoclonal antibody and is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Geometric mean (CV%) clearance was 0.0229 L/hours (34%) and the geometric mean (CV%) elimination half-life was 9.3 days (40%) in subjects with ulcerative colitis. Clearance is independent of dose.

Specific Populations

There were no clinically significant differences in the pharmacokinetics of mirikizumab-mrkz based on age (18 to 79 years), sex, race (White or Asian), or mild and moderate renal impairment (i.e., estimated creatinine clearance by Cockcroft-Gault equation: 30 to 89 mL/min).

Body Weight

Following intravenous administration of 300 mg, the recommended induction dose, in subjects with ulcerative colitis weighing 90 kg or greater, the estimated geometric mean mirikizumab-mrkz average concentration (C_avg) was 20% lower compared with subjects weighing less than 90 kg. Following subcutaneous administration of 200 mg, the recommended maintenance dose, in subjects with ulcerative colitis weighing 90 kg or greater, the estimated geometric mean C_avg was 38% lower compared with subjects weighing less than 90 kg. In Study UC-2 (maintenance), the rate of clinical remission and clinical response did not differ significantly between subjects weighing 90 kg or greater and subjects weighing less than 90 kg.

Drug Interaction Studies

Population pharmacokinetic analyses indicated that the clearance of OMVOH was not impacted by concomitant administration of aminosalicylates, corticosteroids, or oral immunomodulators (6-MP, AZA, MTX, tioguanine) in subjects with ulcerative colitis.

No drug-drug interaction studies were conducted in subjects with ulcerative colitis at the recommended dosage. Based on a clinical drug-drug interaction study conducted in subjects with another condition, multiple subcutaneous doses of 250 mg every 4 weeks of mirikizumab-mrkz (a dosage 1.25-times higher than the recommended maintenance dosage) did not result in changes in the exposure of midazolam (CYP3A substrate), warfarin (CYP2C9 substrate), dextromethorphan (CYP2D6 substrate), omeprazole (CYP2C19 substrate), or caffeine (CYP1A2 substrate).

• 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)].

• OMVOH for intravenous use is intended for administration by a healthcare provider using aseptic technique. Each vial is for single use only.
• 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.
• Using an 18 to 21 gauge needle withdraw 15 mL of OMVOH solution from the vial and transfer to an infusion bag ranging in size from 50 mL to 250 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection. Do not mix with other drugs. Do not dilute or infuse through the same intravenous line with solutions other than 0.9% Sodium Chloride or 5% Dextrose Injection.
• Gently invert the infusion bag to mix the contents. Do not shake the prepared infusion bag.
• Connect the intravenous administration set (infusion line) to the prepared infusion bag and prime the line.
• Administer the infusion over at least 30 minutes.
• At the end of the infusion, flush the line with 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
  • Administer the flush at the same infusion rate as used for OMVOH administration.
  • The time required to flush OMVOH solution from the infusion line is in addition to the minimum 30-minute infusion time.

  Storage of Diluted Solution

  • Start the infusion immediately after preparation. If not used immediately, store the diluted infusion solution in the refrigerator at 2°C to 8°C (36°F to 46°F). Use the diluted infusion solution within 48 total hours, of which not more than 5 hours are permitted at non-refrigerated temperatures not to exceed 25°C (77°F), starting from the time of vial puncture.
  • Keep drug product away from direct heat or light. Do not freeze the diluted solution in the prepared infusion bag.

• A full maintenance dose will require 2 prefilled pens.
• OMVOH is intended for use under the guidance and supervision of a healthcare professional. Patients may self-inject OMVOH after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of OMVOH according to the “Instructions for Use”, included with the packaged product.
• Before injection, remove OMVOH prefilled pen from the refrigerator and leave at room temperature for 30 minutes. Do not shake the prefilled pens.
• 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.
• Sites for injection include the abdomen, thigh, and back of the upper arm. Instruct patients to inject in a different location every time. For example, if the first injection was in the abdomen, administer the second injection (to complete a full dose) in another area of the abdomen, or upper arm, or thigh.
• Do not inject into areas where the skin is tender, bruised, erythematous, or indurated.
• OMVOH does not contain preservatives; therefore, discard any unused product. Do not reuse.
• If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing every 4 weeks.

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

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)].

Serious hypersensitivity reactions, including anaphylaxis during intravenous infusion, have been reported with OMVOH administration. Infusion-related hypersensitivity reactions, including mucocutaneous erythema and pruritis, were reported during induction [see Adverse Reactions (6.1)]. If a severe hypersensitivity reaction occurs, discontinue OMVOH immediately and initiate appropriate treatment.

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.

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.

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 pruritis 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.

Avoid use of live vaccines in patients treated with OMVOH. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with OMVOH, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or non-live vaccines in patients treated with OMVOH.

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)]

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.

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)].

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 1 summarizes the adverse reactions reported in at least 2% of subjects and at a higher frequency than placebo during UC-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 2 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.

Infections

In UC-1 through Week 12, infections were reported by 145 (15%) subjects treated with OMVOH 300 mg and 45 (14%) subjects treated with placebo. Serious infections were reported by less than 1% in both groups. Serious infections in the OMVOH group included intestinal sepsis, listeria sepsis, and pneumonia.

In the maintenance study (UC-2) through Week 40 (a total of 52 weeks of treatment), infections were reported by 93 (24%) subjects treated with OMVOH 200 mg and 44 (23%) subjects treated with placebo. A case of COVID-19 pneumonia was reported as a serious infection in the OMVOH group.

The safety and effectiveness of OMVOH have not been established in pediatric patients.

Of the 795 OMVOH-treated subjects in the two clinical trials, 64 subjects (8%) were 65 years of age and older, while 10 subjects (1%) were 75 years of age and older. These clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger adult subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. No clinically meaningful differences in the pharmacokinetics of mirikizumab-mrkz were observed in subjects 65 years of age and older compared to younger adult subjects [see Clinical Pharmacology (12.3)].

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.

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.

In both study UC-1 (induction) and study UC-2 (maintenance), a positive relationship was observed between mirikizumab-mrkz average concentration and rates of clinical remission and clinical response [see Clinical Studies (14)].

Mirikizumab-mrkz exhibited linear pharmacokinetics with dose-proportional increase in exposure over a dose range of 60 to 2400 mg given as an intravenous injection or over a dose range of 200 to 400 mg given as a subcutaneous injection, in healthy volunteers. There was no apparent accumulation of mirikizumab-mrkz concentrations in serum over time when administered as a subcutaneous injection every 4 weeks to subjects with ulcerative colitis. The estimated exposure parameters of mirikizumab-mrkz at steady state are summarized in Table 3.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of mirikizumab-mrkz or of other mirikizumab products.

During the 52-week treatment period in studies UC-1 and UC-2, 23% (88/378) of OMVOH-treated subjects at the recommended dosage and evaluable for assessment, developed anti-mirikizumab-mrkz antibodies (referred to as anti-drug antibodies (ADA)). Of those who developed ADA, 33/88 (38%) developed titers ≥1:160. Of these 33 OMVOH-treated subjects, 10 had reduced serum trough concentrations of mirikizumab-mrkz compared to subjects who did not develop anti-mirikizumab-mrkz antibodies, and 5 of these 10 subjects did not achieve clinical response at Week 52. There is insufficient data to assess whether the observed ADA-associated pharmacokinetic changes reduced effectiveness. There is no identified clinically significant effect of ADA on the safety of OMVOH over the treatment duration of 52-weeks.

Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of mirikizumab-mrkz.

No organ weight or histopathology effects were observed in the male or female reproductive tract in sexually mature cynomolgus monkeys that received subcutaneous mirikizumab-mrkz once weekly for 26 weeks, at a dose of 100 mg/kg (at least 7 times the MRHD of mirikizumab-mrkz, based on exposure comparisons).

The safety and efficacy of OMVOH was evaluated in two randomized, double-blind, placebo-controlled clinical studies, one induction study [UC-1 (NCT03518086)] and one maintenance study [UC-2 (NCT03524092)], in adult subjects with moderately to severely active ulcerative colitis who had inadequate response, loss of response, or failed to tolerate any of the following: corticosteroids, 6-mercaptopurine, azathioprine, biologic therapy (TNF blocker, vedolizumab), or tofacitinib. The 12-week intravenous induction study (UC-1) was followed by the 40-week subcutaneous randomized withdrawal maintenance study (UC-2).

Study UC-1

In UC-1, efficacy was evaluated in 1062 subjects who were randomized 3:1 at Week 0 to receive 300 mg OMVOH or placebo by intravenous infusion at Week 0, Week 4, and Week 8. Subjects had a mean age of 43 years (range 18 to 79 years); 40% were female; and 71% identified as White, 25% as Asian, 1% as American Indian or Alaska Native, 1% as Black or African American, and <2% as another racial group or did not report their racial group. Subjects were permitted to use stable doses of aminosalicylates, immunomodulators (6-mercaptopurine, azathioprine, methotrexate), and oral corticosteroids (prednisone ≤20 mg/day or equivalent, extended-release budesonide 9 mg/day, beclomethasone dipropionate 5 mg/day). At baseline, 41% of subjects were receiving oral corticosteroids, 24% were receiving immunomodulators, and 75% were receiving aminosalicylates.

At baseline, 57% were biologic and Janus Kinase inhibitor (JAKi) naive, 41% had failed at least one biologic, 3% had failed a JAKi, and 2% had previously received but had not failed a biologic or JAKi.

Disease activity was assessed based on the modified Mayo score (mMS), which ranges from 0 to 9 and has three subscores that are each scored from 0 (normal) to 3 (most severe): stool frequency, rectal bleeding, and findings on centrally read endoscopy subscore. At baseline, subjects had a mMS of 5 to 9, including a centrally read endoscopy subscore of 2 or 3. An endoscopy subscore of 2 was defined by marked erythema, absent vascular pattern, friability, and erosions; and a subscore of 3 was defined by spontaneous bleeding and ulceration. Subjects had a median mMS of 7, and 58% had severely active disease (mMS of 7 to 9).

The primary endpoint was clinical remission at Week 12. The secondary endpoints were clinical response, endoscopic improvement, and histologic-endoscopic mucosal improvement (see Table 4).

Study UC-1 was not designed to evaluate the relationship of histologic-endoscopic mucosal improvement at Week 12 to disease progression and long-term outcomes.

Rectal Bleeding and Stool Frequency Subscores

Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 3 in subjects treated with OMVOH compared to subjects on placebo.

Study UC-2

The maintenance study (UC-2) evaluated 506 subjects who achieved clinical response at Week 12 in Study UC-1. These subjects were randomized 2:1 to receive 200 mg OMVOH or placebo subcutaneously every 4 weeks for 40 weeks in UC-2, for a total of 52 weeks of treatment. Subjects who were on concomitant ulcerative colitis therapies during UC-1 were required to continue on stable doses of oral aminosalicylates and immunomodulators (6-mercaptopurine, azathioprine, methotrexate). Corticosteroid tapering was required for subjects who were receiving corticosteroids at baseline and achieved clinical response in UC-1.

The primary endpoint was clinical remission at Week 40. The secondary endpoints were endoscopic improvement, maintenance of clinical remission in subjects who achieved clinical remission at Week 12, corticosteroid-free clinical remission, and histologic-endoscopic mucosal improvement (see Table 5).

Study UC-2 was not designed to evaluate the relationship of histologic-endoscopic mucosal improvement at Week 40 to disease progression and long-term outcomes.

Bowel Urgency

Bowel urgency was assessed during UC-1 and UC-2 with an Urgency Numeric Rating Scale (NRS) of 0 to 10. A greater proportion of subjects with a baseline Urgency NRS weekly average score ≥3 treated with OMVOH compared to placebo reported an Urgency NRS weekly average score of 0 or 1 (39% versus 23%) at Week 40. Urgency NRS weekly average scores of 0 to 1 were also observed in a greater proportion of subjects treated with OMVOH compared to placebo at Week 12.

Endoscopic Assessment

Normalization of the endoscopic appearance of the mucosa (endoscopic remission) was defined as a Mayo endoscopic subscore of 0. At Week 40 in UC-2, endoscopic remission was observed in a greater proportion of subjects treated with OMVOH compared to placebo (22% versus 14%).

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 as:

Each single-dose prefilled pen consists of a 1 mL glass syringe with a fixed 27-gauge ½ inch 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 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 and prefilled pen are not made with dry natural rubber latex.

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Hypersensitivity Reactions

Advise patients to discontinue OMVOH and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.1)].

Infections

Advise patients that OMVOH may lower the ability of their immune system to fight infections and to contact their healthcare provider immediately if they develop any symptoms of infection [see Warnings and Precautions (5.2)].

Tuberculosis

Advise patients to contact their healthcare provider if they experience symptoms suggestive of TB (e.g., unexplained fever, cough, or difficulty breathing) [see Warnings and Precautions (5.3)].

Hepatotoxicity

Inform patients that OMVOH may cause liver injury. Advise patients to seek immediate medical attention if they experience symptoms suggestive of liver dysfunction (e.g., unexplained rash, nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine) [see Warnings and Precautions (5.4)].

Immunizations

Advise patients that vaccination with live vaccines is not recommended during OMVOH treatment and immediately prior to or after OMVOH treatment. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Instruct patients to inform their healthcare provider that they are taking OMVOH prior to receiving a vaccination [see Warnings and Precautions (5.5)].

Pregnancy

Advise patients who are exposed to OMVOH during pregnancy to contact Eli Lilly and Company [see Use in Specific Populations (8.1)].

Administration

Instruct patients in preparation and administration of OMVOH, including choosing anatomical sites for subcutaneous administration, and proper subcutaneous injection technique. Instruct patients in the technique of pen disposal [see Instructions for Use].

Instruct patients or caregivers to administer two 100 mg prefilled pens to achieve the full 200 mg dose of OMVOH.

Eli Lilly and Company, Indianapolis, IN 46285, USA
US License No. 1891
Copyright © 2023, Eli Lilly and Company. All rights reserved.

OMV-0001-USPI-20231026

OMV-0001-MG-20231026

INSTRUCTIONS FOR USE

OMVOHTM (ahm-VOH)

(mirikizumab-mrkz)

injection, for subcutaneous use

Prefilled Pen

Figure (Omvoh 100mg Ai 1)

This Instructions for Use contains information on how to inject OMVOH.

Before you use the OMVOH prefilled pens (Pens), read and carefully follow all the step-by-step instructions. Two injections are required for a full dose.

Important information you need to know before injecting OMVOH:

For injections under the skin (subcutaneous injection) only.

Your healthcare provider should show you how to prepare and inject OMVOH using the Pen. Do not inject yourself or someone else until you have been shown how to inject OMVOH.

Keep this Instructions for Use and read it as needed.

2 OMVOH injections are required for a full dose.

Inject 1 OMVOH Pen followed right away by the other OMVOH Pen.

Each OMVOH Pen is for 1-time use only.

The OMVOH Pen contains glass parts. Handle it carefully. If you drop it on a hard surface do not use it. Use a new OMVOH Pen for your injection.

Your healthcare provider may help you decide where on your body to inject your dose. You can also read the Choose your injection site section of these instructions to help you choose which area can work best for you.

If you have vision or hearing problems, do not use OMVOH Pen without help from a caregiver.

See Storing OMVOH Pens for important storage information.

INSTRUCTIONS FOR USE

Before you use the OMVOH Pens, read and carefully follow all the step-by-step instructions.

Parts of the OMVOH Pen

Figure (Omvoh 100mg Ai 2)

Important: 2 OMVOH injections are required for a full dose. Inject 1 OMVOH Pen followed right away by the other OMVOH Pen.

Preparing to inject OMVOH
Take the Pens from the refrigerator	Take 2 OMVOH Pens from the refrigerator.
	Leave the gray base caps on until you are ready to inject.
	Leave the Pens at room temperature for 30 minutes before injecting.
	Do not microwave the Pens, or run hot water over them, or leave them in direct sunlight.
	Do not shake the Pens.
Gather supplies	Supplies: 2 alcohol wipes 2 cotton balls or pieces of gauze 1 sharps container (see Throwing away (disposing of) OMVOH Pens)
Inspect the Pens and the medicine             Expiration date Figure (Omvoh 100mg Ai 3)	Make sure you have the right medicine. The medicine inside should be clear. It may be colorless to slightly yellow to slightly brown. Do not use the Pens and throw away (dispose of) as directed by your healthcare provider or pharmacist if: one or both Pens look damaged the medicine is cloudy, is discolored, or has particles the expiration date printed on the label has passed the medicine is frozen
Prepare for injection	Wash your hands with soap and water before you inject OMVOH.
Choose your injection site	Your healthcare provider can help you choose the injection site that is best for you.
Figure (Omvoh Ifu Injection Sites)	You or another person may inject the medicine into your stomach area (abdomen). Do not inject within 2 inches of the belly button (navel).
	You or another person may inject the medicine in the front of your thighs. This area should be at least 2 inches above the knee and 2 inches below the groin.
	Another person may give you the injection in the back of your upper arm.
	Do not inject in the exact same spot every time. For example, if your first injection was in your abdomen, your second injection (to complete a full dose) should be in another spot in your abdomen, or upper arm, or thigh.
	Do not inject into areas where the skin is tender, bruised, red, or hard.
	Clean the injection sites with an alcohol wipe. Let the injection sites dry before you inject the medicine.

Injecting OMVOH
1	Uncap the Pen		Figure (Omvoh 100mg Ai 4) Figure (Omvoh 100mg Ai 5)
	Figure (Omvoh Ai Lock)	Make sure the Pen is locked. Leave the gray base cap on until you are ready to inject.
	Twist off the gray base cap and throw it away in your household trash.
	Do not put the gray base cap back on. This could damage the needle.
	Do not touch the needle.
2	Place and unlock		Figure (Omvoh 100mg Ai 6)
	Place and hold the clear base flat and firmly against the skin.
	Figure (Omvoh Ai Unlock)	Keep the clear base on the skin, then turn the lock ring to the unlock position.
3	Press and hold for up to 10 seconds		Figure (Omvoh 100mg Ai 7)
	Press and hold the blue injection button. You will hear a loud click (injection started).
	Keep holding the clear base firmly against the skin. You will hear a second loud click in about 10 seconds after the first one (injection completed).
	You will know the injection is complete when the gray plunger is visible.
	Remove the Pen from the skin.		Figure (Omvoh 100mg Ai 8)
	If you have bleeding at the injection site, press a cotton ball or gauze over the injection site.
	Do not rub the injection site, as this may cause bruising.
4	Repeat Steps 1 through Step 3 with the second Pen for a full dose. Use the second Pen right after using the first Pen.

Throwing away (disposing of) OMVOH Pens
Throw away the used Pens
Put the used OMVOH Pens in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the OMVOH Pens in your household trash.		Figure (Omvoh 100mg Ai 9)
If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
	made of a heavy-duty plastic,
	can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
	upright and stable during use,
	leak-resistant, and
	properly labeled to warn of hazardous waste inside the container.
When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be local laws about how you should throw away needles and syringes.
For more information about safe sharps disposal, and for specific information about sharps disposal in the state you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
Do not recycle your used sharps disposal container.

Commonly asked questions
Q.	What if I let my Pen warm up for longer than 30 minutes before injecting?
A.	Your Pen can stay at room temperature up to 86°F (30°C) for up to 2 weeks.
Q.	What if I see air bubbles in the Pen?
A.	It is normal to have air bubbles in the Pen. They will not harm you or affect your dose.
Q.	What if there is a drop of liquid on the tip of the needle when I remove the gray base cap?
A.	It is okay to see a drop of liquid on the tip of the needle. This will not harm you or affect your dose.
Q.	What if I unlocked the Pen and pressed the blue injection button before I twisted off the gray base cap?
A.	Do not remove the gray base cap. Throw away (dispose of) the Pen and get a new one.
Q.	Do I need to hold the blue injection button down until the injection is complete?
A.	You do not need to hold the blue injection button down, but it may help you keep the Pen steady and firm against your skin.
Q.	What if the needle did not retract after my injection?
A.	Do not touch the needle or replace the gray base cap. Store the Pen in a safe place to avoid an accidental needlestick and contact 1-800-Lilly-Rx (1-800-545-5979) for instructions on how to return the Pen.
Q.	What if there is a drop of liquid or blood on my skin after my injection?
A.	This is normal. Press a cotton ball or gauze over the injection site. Do not rub the injection site.
Q.	What if I heard more than 2 clicks during my injection – 2 loud clicks and a soft one. Did I get my complete injection?
A.	Some patients may hear a soft click right before the second loud click. That is the normal operation of the Pen. Do not remove the Pen from your skin until you hear the second loud click.
Q.	How can I tell if my injection is complete?
A.	After you press the blue injection button, you will hear 2 loud clicks. The second loud click tells you that your injection is complete. You will also see the gray plunger at the top of the clear base.
If you have more questions about how to use the OMVOH Pen:
	Call your healthcare provider	Figure (Qr V1)	Scan this code to launch www.OMVOH.com
	Call 1-800-Lilly-Rx (1-800-545-5979)
	Visit www.OMVOH.com

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

OMVOH^TM is a trademark of Eli Lilly and Company.

Copyright © 2023, Eli Lilly and Company. All rights reserved.

Issued: October 2023

The OMVOH Pen meets the current dose accuracy and functional requirements of ISO 11608-1 and 11608-5.

OMV-0001-IFU-PEN-20231026

PACKAGE LABEL – Omvoh 300 mg Vial Carton

NDC 0002-7575-01

15 mL

omvoh^TM

(mirikizumab-mrkz)

injection

300 mg/15 mL

(20 mg/mL)

For Intravenous Infusion After Dilution

Single-Dose Vial - Discard Unused Portion

Dispense enclosed Medication Guide to each patient.

Rx only

omvoh.com

Lilly

Package Label – Omvoh 300 mg Vial Carton (Omvoh Carton 300mg Vial 049 00)

PACKAGE LABEL – Omvoh 100 mg Prefilled Pen

NDC 0002-8011-27

omvoh^TM

(mirikizumab-mrkz)

injection

100 mg/mL

For Subcutaneous Use Only

For a 200 mg dose, two 100 mg pens are required. Inject one pen after the other.

2 x 1 mL single-dose prefilled pens

Rx only

Dispense enclosed Medication Guide to each patient.

Lilly

Package Label – Omvoh 100 mg Prefilled Pen (Omvoh Carton 100mg Pen 078 00)