OMVOH 300mg perfusive solution concentrate medication leaflet

Omvoh 300 mg concentrate for solution for infusion

Each vial contains 300 mg mirikizumab in 15 mL solution (20 mg/mL).

After dilution (see section 6.6), the final concentration is approximately 1.1 mg/mL to approximately4.6 mg/mL for the treatment of ulcerative colitis and approximately 3.6 mg/mL to approximately9 mg/mL for the treatment of Crohn’s disease.

Mirikizumab is a humanised monoclonal antibody produced in Chinese Hamster Ovary (CHO) cellsby recombinant DNA technology.

Each 15 mL vial contains approximately 60 mg sodium.

For the full list of excipients, see section 6.1.

Concentrate for solution for infusion (sterile concentrate)

The concentrate is a clear and colourless to slightly yellow solution with a pH of approximately 5.5and an osmolarity of approximately 300 mOsm/L.

Omvoh is indicated for the treatment of adult patients with moderately to severely active ulcerativecolitis who have had an inadequate response with, lost response to, or were intolerant to eitherconventional therapy or a biologic treatment.

Omvoh is indicated for the treatment of adult patients with moderately to severely active Crohn'sdisease who have had an inadequate response with, lost response to, or were intolerant to eitherconventional therapy or a biologic treatment.

This medicinal product is intended for use under the guidance and supervision of a physicianexperienced in the diagnosis and treatment of ulcerative colitis or Crohn’ disease.

Omvoh 300 mg concentrate for solution for infusion should only be used for the induction dose.

The recommended mirikizumab dose regimen has 2 parts.

Induction dose

The induction dose is 300 mg by intravenous infusion for at least 30 minutes at weeks 0, 4 and 8.

The maintenance dose is 200 mg (i.e. two 100 mg pre-filled syringes or two 100 mg pre-filled pens)by subcutaneous injection every 4 weeks after completion of induction dosing.

For the posology of the subcutaneous dosing regimen, see section 4.2 of the Summary of Product

Characteristics for Omvoh 100 mg solution for injection in pre-filled syringe and Omvoh 100 mgsolution for injection in pre-filled pen.

Patients should be evaluated after the 12-week induction dosing and if there is adequate therapeuticresponse, transition to maintenance dosing. For patients who do not achieve adequate therapeuticbenefit at week 12 of induction dosing, mirikizumab 300 mg by intravenous infusion may becontinued at weeks 12, 16 and 20 (extended induction therapy). If therapeutic benefit is achievedwith the additional intravenous therapy, patients may initiate mirikizumab subcutaneous maintenancedosing (200 mg) every 4 weeks, starting at week 24. Mirikizumab should be discontinued in patientswho do not show evidence of therapeutic benefit to extended induction therapy by week 24.

Patients with loss of therapeutic response during maintenance treatment may receive 300 mgmirikizumab by intravenous infusion every 4 weeks, for a total of 3 doses (re-induction). If clinicalbenefit is achieved from this additional intravenous therapy, patients may resume mirikizumabsubcutaneous dosing every 4 weeks. The efficacy and safety of repeated re-induction therapy havenot been evaluated.

The recommended mirikizumab dose regimen has 2 parts.

Induction dose

The induction dose is 900 mg (3 vials of 300 mg each) by intravenous infusion for at least90 minutes at weeks 0, 4 and 8.

The maintenance dose is 300 mg (i.e. one pre-filled syringe or pre-filled pen of 100 mg and onepre-filled syringe or pre-filled pen of 200 mg) by subcutaneous injection every 4 weeks aftercompletion of induction dosing.

The injections may be administered in any order.

The 200 mg pre-filled syringe and 200 mg pre-filled pen are only for the treatment of Crohn’sdisease.

For the posology of the subcutaneous dosing regimen, see section 4.2 of the Summary of Product

Characteristics for Omvoh solutions for injection in pre-filled syringe and pre-filled pen.

Consideration should be given to discontinuing treatment in patients who have shown no evidence oftherapeutic benefit by week 24.

No dose adjustment is required (see section 5.2). There is limited information in subjects aged≥ 75 years.

Omvoh has not been studied in these patient populations. These conditions are generally notexpected to have any significant impact on the pharmacokinetics of monoclonal antibodies and nodose adjustments are considered necessary (see section 5.2).

The safety and efficacy of Omvoh in children and adolescents aged 2 to less than 18 years have notyet been established. No data are available.

There is no relevant use of Omvoh in children below 2 years for the indication of ulcerative colitis or

Omvoh 300 mg concentrate for solution for infusion is for intravenous use only. Each vial is forsingle use only.

For instructions on dilution of the medicinal product before administration, see section 6.6.

Administration of the diluted solution

* The intravenous administration set (infusion line) should be connected to the preparedintravenous bag and the line should be primed.o For ulcerative colitis the infusion should be administered for at least 30 minutes.o For Crohn’s disease the infusion should be administered for at least 90 minutes.

* At the end of the infusion, to ensure a full dose is administered, the infusion line should beflushed with sodium chloride 9 mg/mL (0.9 %) solution or 5 % glucose solution for injection.

The flush should be administered at the same rate as used for Omvoh administration. The timerequired to flush Omvoh solution from the infusion line is in addition to the minimum30 minutes (ulcerative colitis) or 90 minutes (Crohn’s disease) infusion time.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Clinically important active infections (active tuberculosis).

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

In clinical studies, hypersensitivity reactions have been reported. Most were mild or moderate,severe reactions were uncommon (see section 4.8). If a serious hypersensitivity reaction, includinganaphylaxis, occurs, mirikizumab must be discontinued immediately and appropriate therapy mustbe initiated.

Mirikizumab may increase the risk of severe infection (see section 4.8). Treatment with mirikizumabshould not be initiated in patients with a clinically important active infection until the infectionresolves or is adequately treated (see section 4.3). The risks and benefits of treatment should beconsidered prior to initiating use of mirikizumab in patients with a chronic infection or a history ofrecurrent infection. Patients should be instructed to seek medical advice if signs or symptoms ofclinically important acute or chronic infection occur. If a serious infection develops, discontinuationof mirikizumab should be considered until the infection resolves.

Pre-treatment evaluation for tuberculosis

Prior to initiating treatment, patients should be evaluated for tuberculosis (TB) infection. Patientsreceiving mirikizumab should be monitored for signs and symptoms of active TB during and aftertreatment. Anti-TB therapy should be considered prior to initiating treatment in patients with a pasthistory of latent or active TB in whom an adequate course of treatment cannot be confirmed.

Hepatic enzyme elevations

Cases of drug-induced liver injury (including one case meeting Hy’s Law criteria) occurred inpatients receiving mirikizumab in clinical trials. Liver enzymes and bilirubin should be evaluated atbaseline and monthly during induction (including extended induction period, if applicable).

Thereafter, liver enzymes and bilirubin should be monitored (every 1 - 4 months) according tostandard practice for patient management and as clinically indicated. If increases in alanineaminotransferase (ALT) or aspartate aminotransferase (AST) are observed and drug-induced liverinjury is suspected, mirikizumab must be discontinued until this diagnosis is excluded.

Prior to initiating therapy with mirikizumab, completion of all appropriate immunisations should beconsidered according to current immunisation guidelines. Avoid use of live vaccines in patientstreated with mirikizumab. No data are available on the response to live or non-live vaccines.

This medicinal product contains 60 mg sodium per 300 mg dose, equivalent to 3 % of the WHOrecommended maximum daily intake of 2 g sodium for an adult.

If prepared with sodium chloride 9 mg/mL (0.9 %) solution for injection, the amount of sodiumcontributed by the sodium chloride diluent will range from 177 mg (for a 50 mL bag) to 885 mg (fora 250 mL bag), equivalent to 9-44 % of the WHO recommended maximum daily intake. This is inaddition to the amount contributed by the medicinal product.

This medicinal product contains 180 mg sodium per 900 mg dose, equivalent to 9 % of the WHOrecommended maximum daily intake of 2 g sodium for an adult.

If prepared with sodium chloride 9 mg/mL (0.9 %) solution for injection, the amount of sodiumcontributed by the sodium chloride diluent will range from 195 mg (for a 100 mL bag) to 726 mg(for a 250 mL bag), equivalent to 10-36 % of the WHO recommended maximum daily intake. This isin addition to the amount contributed by the medicinal product.

Polysorbate

This medicinal product contains 0.5 mg/mL of polysorbate 80 in each vial which is equivalent to7.5 mg for the induction dose to treat ulcerative colitis and equivalent to 22.5 mg for the inductiondose to treat Crohn’s disease. Polysorbates may cause allergic reactions.

No interaction studies have been performed.

In clinical studies, concomitant use of corticosteroids or oral immunomodulators did not influencethe safety of mirikizumab.

Population pharmacokinetic data analyses indicated that the clearance of mirikizumab was notimpacted by concomitant administration of 5-ASAs (5-aminosalicylic acid), corticosteroids or oralimmunomodulators (azathioprine, 6-mercaptopurine, thioguanine, and methotrexate).

Women of childbearing potential should use an effective method of contraception during treatmentand for at least 10 weeks after treatment.

There is a limited amount of data from the use of mirikizumab in pregnant women. Animal studiesdo not indicate direct or indirect harmful effects with respect to reproductive toxicity (seesection 5.3). As a precautionary measure, it is preferable to avoid the use of Omvoh duringpregnancy.

It is unknown whether mirikizumab is excreted in human milk. Human IgGs are known to beexcreted in breast milk during the first few days after birth, which is decreasing to lowconcentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excludedduring this short period. A decision must be made whether to discontinue breast-feeding or todiscontinue/abstain from Omvoh therapy taking into account the benefit of breast feeding for thechild and the benefit of therapy for the woman.

The effect of mirikizumab on human fertility has not been evaluated (see section 5.3).

Omvoh has no or negligible influence on the ability to drive and use machines.

The most frequently reported adverse reactions are upper respiratory tract infections (9.8 %, mostfrequently nasopharyngitis), headache (3.2 %), rash (1.3 %) and injection site reactions (10.8 %,maintenance period).

Adverse reactions from clinical studies (Table 1) are listed by MedDRA system organ class. Thefrequency category for each reaction is based on the following convention: very common (≥ 1/10);common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); veryrare (< 1/10 000).

Table 1: Adverse reactions

MedDRA System organ class Frequency Adverse reaction

Infections and infestations Common Upper respiratory tract infectionsa

Uncommon Herpes zoster

Immune system disorders Uncommon Infusion-related hypersensitivity reactions

Musculoskeletal and Connective Common Arthralgia

Tissue Disorders

Nervous system disorders Common Headache

Skin and subcutaneous tissue Common Rashbdisorders

General disorders and Very common Injection site reactionscadministration site conditions Uncommon Infusion site reactionsd

Investigations Uncommon Alanine aminotransferase increased

Uncommon Aspartate aminotransferase increaseda Includes: acute sinusitis, COVID-19, nasopharyngitis, oropharyngeal discomfort, oropharyngealpain, pharyngitis, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection, and viral upperrespiratory tract infection.

b Includes: rash, rash macular, rash maculo-papular, and rash papular and rash pruritic.c Reported during mirikizumab maintenance therapy where mirikizumab treatment is administeredas subcutaneous injection.d Reported during mirikizumab induction therapy where mirikizumab treatment is administered asintravenous infusion.

Infusion-related hypersensitivity reactions (induction therapy)

Infusion-related hypersensitivity reactions were reported in 0.4 % of mirikizumab-treated patients.

All infusion-related hypersensitivity reactions were reported as non-serious.

Injection site reactions (maintenance therapy)

Injection site reactions were reported in 10.8 % of mirikizumab-treated patients. The most frequentreactions were injection site pain, injection site reaction and injection site erythema. These symptomswere reported as non-serious, mild and transient in nature.

The results described above were obtained with the original formulation of Omvoh. In a doubleblind, 2-arm, randomised, single-dose, parallel design study in 60 healthy subjects comparing200 mg mirikizumab (2 injections of 100 mg in a pre-filled syringe) of the original formulation withthe revised formulation statistically significantly lower VAS pain scores were obtained with therevised (12.6) vs. the original formulation (26.1) 1 minute after injection.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased

In the first 12 weeks, ALT increased was reported in 0.6 % mirikizumab-treated patients. ASTincreased was reported by 0.4 % mirikizumab-treated patients. All adverse reactions were reported asmild to moderate in severity and non-serious.

Overall mirikizumab treatment periods in the ulcerative colitis and Crohn’s disease clinicaldevelopment program (including the placebo-controlled and open label induction and maintenanceperiods), there have been elevations of ALT to ≥ 3 x upper limit of normal (ULN) (2.3 %),≥ 5 x ULN (0.7 %) and ≥ 10 x ULN (0.2 %) and AST to ≥ 3 x ULN (2.2 %), ≥ 5 x ULN (0.8 %) and≥ 10 x ULN (0.1 %) in patients receiving mirikizumab (see section 4.4). These elevations have beennoted with and without concomitant elevations in total bilirubin.

In the ulcerative colitis studies, up to 23 % of mirikizumab-treated patients with 12 months oftreatment developed anti-drug antibodies, most of which were of low titer and tested positive forneutralising activity. Higher antibody titers in approximately 2 % of subjects treated withmirikizumab were associated with lower serum mirikizumab concentrations and reduced clinicalresponse.

In the Crohn’s disease study, 12.7% of mirikizumab-treated patients with 12 months of treatmentdeveloped anti-drug antibodies, most of which were of low titer and tested positive for neutralisingactivity. There was no identified clinically significant effect of anti-drug antibodies onpharmacokinetics or effectiveness of mirikizumab.

No association was found between anti-mirikizumab antibodies and hypersensitivity or injection-related events in either the ulcerative colitis or the Crohn’s disease studies.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Mirikizumab doses up to 2 400 mg intravenously and up to 500 mg subcutaneously have beenadministered in clinical trials without dose-limiting toxicity. In the event of overdose, the patientmust be monitored for signs or symptoms of adverse reactions and appropriate symptomatictreatment must be started immediately.

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC24

Mirikizumab is a humanised IgG4 monoclonal, anti-interleukin-23 (anti-IL-23) antibody thatselectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the

IL-23 receptor.

IL-23, a regulatory cytokine, affects the differentiation, expansion, and survival of T cell subsets,(e.g., Th17 cells and Tc17 cells) and innate immune cell subsets, which represent sources of effectorcytokines, including IL-17A, IL-17F and IL-22 that drive inflammatory disease. In humans, selectiveblockade of IL-23 was shown to normalise production of these cytokines.

Inflammatory biomarkers were measured in the phase 3 ulcerative colitis and Crohn’s diseasestudies. Mirikizumab administered intravenously every 4 weeks during induction dosingsignificantly reduced levels of fecal calprotectin and C-reactive protein from baseline to week 12.

Also, mirikizumab administered subcutaneously every 4 weeks during maintenance dosing sustainedsignificantly reduced levels of fecal calprotectin and C-reactive protein up to 52 weeks.

The efficacy and safety of mirikizumab was evaluated in adult patients with moderately to severelyactive ulcerative colitis in two randomised, double-blind, placebo-controlled, multicentre studies.

Enrolled patients had a confirmed diagnosis of ulcerative colitis for at least 3 months and moderatelyto severely active disease, defined as a modified Mayo score of 4 to 9, including a Mayo endoscopysubscore ≥ 2. Patients had to have failed (defined as loss of response, inadequate response orintolerance) corticosteroids or immunomodulators (6-mercaptopurine, azathioprine) or at least onebiologic (a TNFα antagonist and/or vedolizumab) or tofacitinib.

LUCENT-1 was an intravenous induction study with treatment of up to 12 weeks, followed by a40 week subcutaneous randomised withdrawal maintenance study (LUCENT-2), representing at least52 weeks of therapy. Mean age was 42.5 years. 7.8 % of patients were ≥ 65 of age and 1.0 % ofpatients ≥ 75 of age. 59.8 % were men; 40.2 % were women. 53.2 % had severely active disease witha modified Mayo score 7 to 9.

Efficacy results presented for LUCENT-1 and LUCENT-2 were based on central reading ofendoscopies and histology.

LUCENT-1

LUCENT-1 included 1 162 patients in the primary efficacy population. Patients were randomised toreceive a dose of 300 mg mirikizumab via intravenous infusion or placebo, at week 0, week 4 andweek 8 with a 3:1 treatment allocation ratio. The primary endpoint for the induction study was theproportion of subjects in clinical remission [modified Mayo score (MMS) defined as: Stoolfrequency (SF) subscore = 0 or 1 with a ≥ 1-point decrease from baseline, and rectal bleeding (RB)subscore = 0, and Endoscopic subscore (ES) = 0 or 1 (excluding friability)] at week 12.

Patients in these studies may have received other concomitant therapies includingaminosalicylates (74.3 %), immunomodulatory agents (24.1 % such as azathioprine,6-mercaptopurine or methotrexate), and oral corticosteroids (39.9 %; prednisone daily dose up to20 mg or equivalent) at a stable dose prior to and during the induction period. Per protocol oralcorticosteroids were tapered after induction.

Of the primary efficacy population, 57.1 % were biologic-naive and tofacitinib-naive. 41.2 % ofpatients had failed a biologic or tofacitinib. 36.3 % of the patients had failed at least 1 prior anti-TNFtherapy, 18.8 % had failed vedolizumab and 3.4 % of patients had failed tofacitinib. 20.1 % hadfailed more than one biologic or tofacitinib. An additional 1.7 % had previously received but had notfailed a biologic or tofacitinib.

In LUCENT-1 a significantly greater proportion of patients were in clinical remission in themirikizumab treated group compared to placebo at week 12 (Table 2). As early as week 2,mirikizumab-treated patients achieved a greater reduction in RB subscores and decreases in SFsubscores.

Table 2: Summary of key efficacy outcomes in LUCENT-1 (week 12 unless indicatedotherwise)

Placebo Mirikizumab IVn = 294 n = 868 Treatmentdifferencen % n % and 99.875 % CI

Clinical remission*1 39 13.3 % 210 24.2 % 11.1 %(3.2 %, 19.1 %)c

Patients who were biologic and

JAK-inhibitor naïve a 27/171 15.8 % 152/492 30.9 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 10/118 8.5 % 55/361 15.2 % - - -

Alternate clinical remission*2 43 14.6 % 222 25.6 % 11.1 %(3.0 %, 19.3 %)c

Patients who were biologic and

JAK-inhibitor naïve a 31/171 18.1 % 160/492 32.5 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 10/118 8.5 % 59/361 16.3 % - - -

Clinical response*3 124 42.2 % 551 63.5 % 21.4 %(10.8 %, 32.0 %)c

Patients who were biologic and

JAK-inhibitor naïve a 86/171 50.3 % 345/492 70.1 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 35/118 29.7 % 197/361 54.6 % - - -

Endoscopic improvement*4 62 21.1 % 315 36.3 % 15.4 %(6.3 %, 24.5 %)c

Patients who were biologic and

JAK-inhibitor naïve a 48/171 28.1 % 226/492 45.9 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 12/118 10.2 % 85/361 23.5 % - - -

Symptomatic remission(week 4)*5 38 12.9 % 189 21.8 % 9.2 %(1.4 %, 16.9 %)c

Patients who were biologic and

JAK-inhibitor naïve a 26/171 15.2 % 120/492 24.4 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 10/118 8.5 % 67/361 18.6 % - - -

Symptomatic remission*5 82 27.9 % 395 45.5 % 17.5 %(7.5 %, 27.6 %)c

Patients who were biologic and

JAK-inhibitor naïve a 57/171 33.3 % 248/492 50.4 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 22/118 18.6 % 139/361 38.5 % - - -

Histo-endoscopic mucosalimprovement*6 41 13.9 % 235 27.1 % 13.4 %(5.5 %, 21.4 %)c

Patients who were biologic and

JAK-inhibitor naïve a 32/171 18.7 % 176/492 35.8 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 8/118 6.8 % 56/361 15.5 % - - -

Placebo Mirikizumab IVn = 294 n = 868 Treatmentdifference

LS Standard LS Standard and 99.875 % CImean error mean error

Bowel urgency severity*7 -1.63 0.141 -2.59 0.083 -0.95(-1.47, -0.44)c

Patients who were biologic and

JAK-inhibitor naïve a -2.08 0.174 -2.72 0.101 - - -

Patients who failed b at leastone biologic or JAK-inhibitor d -0.95 0.227 -2.46 0.126 - - -

Abbreviations: CI = confidence interval; IV = intravenous; LS = least square

*1 Clinical remission is based on the modified Mayo score (MMS) and is defined as: Stool frequency(SF) subscore = 0 or 1 with a ≥ 1-point decrease from baseline, and Rectal bleeding (RB)subscore = 0, and Endoscopic subscore (ES) = 0 or 1 (excluding friability)

*2 Alternate clinical remission is based on the modified Mayo score (MMS) and is defined as: Stoolfrequency (SF) subscore = 0 or 1, and Rectal bleeding (RB) subscore = 0, and Endoscopicsubscore (ES) = 0 or 1 (excluding friability)

*3 Clinical response based on the MMS and is defined as: A decrease in the MMS of ≥ 2 points and≥ 30 % decrease from baseline, and a decrease of ≥ 1 point in the RB subscore from baseline or a

RB score of 0 or 1

*4 Endoscopic improvement defined as: ES = 0 or 1 (excluding friability)

*5 Symptomatic remission defined as: SF = 0, or SF = 1 with a ≥ 1-point decrease from baseline,and RB = 0

*6 Histo-endoscopic mucosal improvement defined as achieving both: 1. Histologic improvement,defined using Geboes scoring system with neutrophil infiltration in < 5 % of crypts, no cryptdestruction, and no erosions, ulcerations, or granulation tissue. 2. Endoscopic improvement,defined as ES = 0 or 1 (excluding friability).

*7 Change from baseline in the Urgency Numeric Rating Scale scorea) An additional 5 patients on placebo and 15 patients on mirikizumab where previously exposed tobut did not fail a biologic or JAK-inhibitor.b) Loss of response, inadequate response or intolerance.c) p < 0.001d) Mirikizumab results in the subgroup of patients who failed more than one biologic or

JAK-inhibitor were consistent with results in the overall population.

LUCENT-2

LUCENT-2 evaluated 544 patients out of the 551 patients who achieved clinical response withmirikizumab in LUCENT-1 at week 12 (see Table 2). Patients were re-randomised in a 2:1 treatmentallocation ratio to receive a subcutaneous maintenance regimen of 200 mg mirikizumab or placeboevery 4 weeks for 40 weeks (which is 52 weeks from initiation of the induction dose). The primaryendpoint for the maintenance study was the proportion of subjects in clinical remission (samedefinition as in LUCENT-1) at week 40. Corticosteroid tapering was required upon entrance into

LUCENT-2 for patients who were receiving corticosteroids during LUCENT-1. Significantly greaterproportions of patients were in clinical remission in the mirikizumab-treated group compared to theplacebo group at week 40 (see Table 3).

Table 3: Summary of key efficacy measures in LUCENT-2 (week 40; 52 weeks from initiationof the induction dose)

Placebo Mirikizumab SC Treatmentn = 179 n = 365 difference and95 % CIn % n %

Clinical remission*1 45 25.1 % 182 49.9 % 23.2 %(15.2 %, 31.2 %)c

Patients who were biologicand JAK-inhibitor naïve a 35/114 30.7 % 118/229 51.5 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 10/64 15.6 % 59/128 46.1 % - - -

Alternate clinical remission*2 47 26.3 % 189 51.8 % 24.1 %(16.0 %, 32.2 %)c

Patients who were biologicand JAK-inhibitor naïve a 37/114 32.5 % 124/229 54.1 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 10/64 15.6 % 60/128 46.9 % - - -

Maintenance of clinical 24.8 %remission through week 40*3 24/65 36.9 % 91/143 63.6 %(10.4 %, 39.2 %)c

Patients who were biologicand JAK-inhibitor naïve a 22/47 46.8 % 65/104 62.5 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 2/18 11.1 % 24/36 66.7 % - - -

Corticosteroid-free remission*4 39 21.8 % 164 44.9 % 21.3 %(13.5 %, 29.1 %)c

Patients who were biologicand JAK-inhibitor naïve a 30/114 26.3 % 107/229 46.7 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 9/64 14.1 % 52/128 40.6 % - - -

Endoscopic improvement*5 52 29.1 % 214 58.6 % 28.5 %(20.2 %, 36.8 %)c

Patients who were biologicand JAK-inhibitor naïve a 39/114 34.2 % 143/229 62.4 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 13/64 20.3 % 65/128 50.8 % - - -

Histo-endoscopic mucosalremission*6 39 21.8 % 158 43.3 % 19.9 %(12.1 %, 27.6 %)c

Patients who were biologicand JAK-inhibitor naïve a 30/114 26.3 % 108/229 47.2 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 9/64 14.1 % 46/128 35.9 % - - -

Bowel urgency remission*7 43/172 25.0 % 144/336 42.9 % 18.1 %(9.8 %, 26.4 %)c

Patients who were biologicand JAK-inhibitor naïve a 31/108 28.7 % 96/206 46.6 % - - -

Patients who failed b at leastone biologic or JAK-inhibitor d 12/63 19.0 % 43/122 35.2 % - - -

Placebo Mirikizumab SC Treatmentn = 179 n = 365 difference and95 % CI

LS Standard LS Standardmean error mean error

Bowel urgency severity*8 -2.74 0.202 -3.80 0.139 -1.06(-1.51, -0.61)c

Patients who were biologicand JAK-inhibitor naïve a -2.69 0.233 -3.82 0.153 - - -

Patients who failed b at leastone biologic or JAK-inhibitor d -2.66 0.346 -3.60 0.228 - - -

Abbreviations: CI = confidence interval; SC = subcutaneous; LS = least square

*1, 2 See footnotes on Table 2

*3 The proportion of patients who were in clinical remission at week 40 among patients in clinicalremission at week 12, with clinical remission defined as: Stool frequency (SF) subscore = 0 or

SF = 1 with a ≥ 1-point decrease from induction baseline, and Rectal bleeding (RB)subscore = 0, and Endoscopic subscore (ES) = 0 or 1 (excluding friability)

*4 Corticosteroid-free remission without surgery, defined as: Clinical remission at week 40, and

Symptomatic remission at week 28, and no corticosteroid use for ≥ 12 weeks prior to week 40

*5 Endoscopic improvement defined as: ES = 0 or 1 (excluding friability)

*6 Histo-endoscopic mucosal remission, defined as achieving both: 1. Histologic remission, definedas Geboes subscores of 0 for grades: 2b (lamina propria neutrophils), and 3 (neutrophils inepithelium), and 4 (crypt destruction), and 5 (erosion or ulceration) and 2. Mayo endoscopicscore 0 or 1 (excluding friability)

*7 Numeric Rating Scale (NRS) 0 or 1 in patients with urgency NRS ≥ 3 at baseline in LUCENT-1

*8 Change from baseline in the Urgency NRS scorea) An additional 1 patient on placebo and 8 patients on mirikizumab where previously exposed tobut did not fail a biologic or JAK-inhibitor.b) Loss of response, inadequate response or intolerance.c) p < 0.001d) Mirikizumab results in the subgroup of patients who failed more than one biologic or

JAK-inhibitor were consistent with results in the overall population.

The efficacy and safety profile of mirikizumab was consistent across subgroups, i.e. age, gender,body weight, disease activity severity at baseline and region. The effect size may vary.

At week 40, a greater proportion of patients were in clinical response (defined as decrease in the

MMS of ≥ 2 points and ≥ 30 % decrease from baseline, and a decrease of ≥ 1 point in the RBsubscore from baseline or a RB score of 0 or 1) in the mirikizumab responder group re-randomisedto mirikizumab (80 %) compared to the mirikizumab responder group re-randomised to placebo(49 %).

Week 24 responders to mirikizumab extended induction (LUCENT-2)

For the mirikizumab patients who were not in response at week 12 of LUCENT-1 and receivedopen-label additional 3 doses of 300 mg mirikizumab IV every 4 weeks (Q4W) 53.7 % achievedclinical response at week 12 of LUCENT-2 and 52.9 % mirikizumab patients continued tomaintenance receiving 200 mg mirikizumab Q4W SC, and among these patients 72.2 % achievedclinical response and 36.1 % achieved clinical remission at week 40.

Recapture of efficacy after loss of response to mirikizumab maintenance (LUCENT-2)19 patients who experienced a first loss of response (5.2 %) between week 12 and 28 of LUCENT-2received open-label mirikizumab rescue dosing with 300 mg mirikizumab Q4W IV for 3 doses and12 of these patients (63.2 %) achieved symptomatic response and 7 patients (36.8 %) achievedsymptomatic remission after 12 weeks.

Endoscopic normalisation at week 40

Normalisation of endoscopic appearance of the mucosa was defined as a Mayo endoscopic subscoreof 0. At week 40 of LUCENT-2, endoscopic normalisation was achieved in 81/365 (22.2 %) ofpatients treated with mirikizumab and in 24/179 (13.4 %) of patients in placebo group.

Histologic outcomes

At week 12 greater proportions of patients in the mirikizumab group achieved histologicimprovement (39.2 %) compared with patients in the placebo group (20.7 %). At week 40 histologicremission was observed with more patients in the mirikizumab group (48.5 %) as compared toplacebo (24.6 %).

Stable maintenance of symptomatic remission

Stable maintenance of symptomatic remission was defined as the proportion of patients insymptomatic remission for at least 7 out of 9 visits from week 4 to week 36 and in symptomaticremission at week 40 among patients in symptomatic remission and clinical response at week 12 of

LUCENT-1. At week 40 of LUCENT-2, the proportion of patients achieving stable maintenance ofsymptomatic remission was greater in patients treated with mirikizumab (69.7 %) versus placebo(38.4 %).

At week 12 of LUCENT-1, patients receiving mirikizumab showed significantly greater clinicallyrelevant improvements on the Inflammatory Bowel Disease Questionnaire (IBDQ) total score(p ≤ 0.001) when compared to placebo. IBDQ response was defined as at least a 16-pointimprovement from baseline in IBDQ score and IBDQ remission was defined as a score of atleast 170. At week 12 of LUCENT-1, 57.5 % of mirikizumab-treated patients achieved IBDQremission versus 39.8 % with placebo (p < 0.001) and 72.7 % of mirikizumab-treated patientsachieved IBDQ response versus 55.8 % in placebo. In LUCENT-2 at week 40, 72.3 % ofmirikizumab-treated patients achieved maintenance of IBDQ remission versus 43.0 % placebotreated patients and 79.2 % mirikizumab treated patients achieved IBDQ response versus 49.2 % ofplacebo treated patients.

Decreases in bowel urgency severity were observed as early as week 2 in patients treated withmirikizumab in LUCENT-1. Patients receiving mirikizumab achieved significant bowel urgencyremission compared with patients in the placebo group at week 12 in LUCENT-1 (22.1 % vs12.3 %), and week 40 in LUCENT-2 (42.9 % vs 25 %). Patients receiving mirikizumab showedsignificant improvements in fatigue as early as week 2 of LUCENT-1 and the improvements weremaintained at week 40 of LUCENT-2. As early as week 4 there was also a significantly greaterreduction in abdominal pain.

Hospitalisations and ulcerative colitis related surgeries

Through week 12 of LUCENT-1, the proportion of patients with UC-related hospitalisations were0.3 % (3/868) in the mirikizumab and 3.4 % (10/294) in the placebo group. UC-related surgerieswere reported in 0.3 % (3/868) patients receiving mirikizumab and 0.7 % (2/294) patients in theplacebo group. There were no UC-related hospitalisations and no UC-related surgeries in

LUCENT-2 in the mirikizumab arm.

The efficacy and safety of mirikizumab was evaluated in a randomized, double-blind, placebo- andactive controlled treat-through designed clinical study VIVID-1 in adult patients with moderately toseverely active Crohn’s disease who had an inadequate response with, loss of response, orintolerance to corticosteroids, immunomodulators (e.g. azathioprine, 6-mercaptopurine), or abiologic treatment (e.g. TNFα antagonist or integrin receptor antagonist). This study included amirikizumab 12-week intravenous infusion induction period followed by a 40-week subcutaneousinjection maintenance period. This study also included an ustekinumab comparator arm in theinduction and maintenance periods.

VIVID-1

In VIVID-1, efficacy was evaluated in 1065 patients who were randomized 6:3:2 to receivemirikizumab 900 mg by intravenous infusion (IV) at week 0, week 4, and week 8 followed by amaintenance dose of 300 mg by subcutaneous injection (SC) at week 12 and then every 4 weeks(Q4W) for 40 weeks, ustekinumab approximately 6 mg/kg by IV administration at week 0 followedby 90 mg SC administration every 8 weeks (Q8W) starting at week 8, or placebo. Patientsrandomised to placebo at baseline who achieved clinical response by Patient-Reported Outcome(PRO) at week 12 (defined as at least a 30% decrease in stool frequency (SF) and/or abdominal pain(AP) with neither score worse than baseline) remained on placebo. Patients randomized to placebo atbaseline who did not achieve clinical response by PRO at week 12 received mirikizumab 900 mg by

IV infusion at week 12, week 16, and week 20 followed by a maintenance dose of 300 mg Q4W SCat week 24 through week 48.

Disease activity at baseline was assessed by (1) the unweighted daily average of SF (2), theunweighted daily average AP (ranging from 0 to 3) and (3) Simple Endoscopic Score for Crohn’sdisease (SES-CD) (ranging from 0 to 56).

Moderately to severely active CD was defined by SF ≥4 and/or AP ≥2 and SES-CD ≥7 (centrallyread) for patients with ileal-colonic and isolated colonic disease or ≥4 for patients with isolated ilealdisease. At baseline patients had a median SF of 6, AP of 2 and SES-CD of 12.

Patients had a mean age of 36 years (range 18 to 76 years); 45 % were female; and 72 % identified as

White, 25 % as Asian, 2 % as Black, and 1 % as another racial group. Patients were permitted to usestable doses of corticosteroids, immunomodulators (e.g., 6-mercatopurine, azathioprine ormethotrexate) and/or aminosalicylates. At baseline, 31 % of patients were receiving oralcorticosteroids, 27 % were receiving immunomodulators, and 44 % were receiving aminosalicylates.

At baseline, 49 % had a loss of response, inadequate response, or intolerance to one or more biologictherapy (prior biologic failure); 46 % of patients had failed TNFα inhibitors and 11 % had failedvedolizumab therapy.

The co-primary endpoints of VIVID-1 were (1) clinical response by PRO at week 12 and endoscopicresponse at week 52 versus placebo and (2) clinical response by PRO at week 12 and clinicalremission by Crohn’s Disease Activity Index (CDAI) at week 52; the results for the co-primaryendpoints and the major secondary endpoints at week 52 versus placebo are provided in table 4.

The major secondary endpoints at week 12 versus placebo are provided in table 5.

Table 4. Proportion of patients with Crohn’s disease meeting efficacy endpoints in VIVID-1 atw eek 52

Placebo Mirikizumab Treatmentn=199 300 mg SC Difference frominjectiona Placebobn=579 (99.5% CI)n % n %

Co-primary endpoints

Clinical response by PROc at week 12 and 18/199 9 % 220/579 38 % 29%e (21 %, 37 %)endoscopic responsed at week 52

Without prior biologic failure 12/102 12 % 117/298 39 %

Prior biologic failuref 6/97 6 % 103/281 37 %

Clinical response by PROc at week 12 and 39/199 20 % 263/579 45 % 26 %e (16 %, 36 %)clinical remission by CDAIg at week 52

Without prior biologic failure 27/102 27 % 141/298 47 %

Prior biologic failuref 12/97 12 % 122/281 43 %

Additional endpoints

Endoscopic responsed at week 52 18/199h 9 % 280/579 48 % 39 %e (31 %, 47 %)

Without prior biologic failure 12/102h 12 % 154/298 52 %

Prior biologic failuref 6/97h 6 % 126/281 45 %

Clinical remission by CDAIh at week 52 39/199h 20 % 313/579 54 % 35 %e (25 %, 44 %)

Without prior biologic failure 27/102h 27 % 169/298 57 %

Prior biologic failuref 12/97h 12 % 144/281 51 %

Clinical response by PROc at week 12 and 39/199 20 % 263/579 45 % 26 %e (16 %, 36 %)clinical remission by PROi at week 52

Clinical response by PROc at week 12 and 8/199 4 % 136/579 24 % 19 %e (13 %, 26 %)endoscopic remissionj at week 52

Clinical response by PROc at week 12 and 37/199 19 % 253/579 44 % 25 %e (15 %, 35 %)corticosteroid-free clinical remission by

CDAIg, k at Week 52

Abbreviations: AP = abdominal pain; CDAI = Crohn’s Disease Activity Index; CI = confidenceinterval; PRO = 2 of the patient-reported items of the CDAI (SF and AP); SES-CD = Simple

Endoscopic Score for Crohn’s Disease; SF = stool frequency.a Following mirikizumab 900 mg as an IV infusion at week 0, week 4, and week 8 patientsreceived mirikizumab 300 mg as a SC injection at week 12 and every 4 weeks thereafter for up toan additional 40 weeks.

b For binary endpoints adjusted treatment difference was based on Cochran-Mantel-Haenszelmethod adjusted for baseline covariates.

c Clinical response by PRO is defined as at least a 30% decrease in SF and/or AP and neither scoreworse than baseline.

d Endoscopic response is defined as ≥50% reduction from baseline in SES-CD total score, based oncentral reading.

e p <0.000001f Prior biologic failure includes loss of response, inadequate response, or intolerance to one ormore biologic therapy (e.g. TNFα antagonist or integrin receptor antagonist).g Clinical remission by CDAI is defined as CDAI total score < 150.h Placebo sample size includes all patients randomized to placebo at baseline. Placebo patients thatdid not achieve clinical response by PRO at week 12 were considered non-responders at week 52.i Clinical remission by PRO is defined as SF ≤3 and not worse than baseline (according to the

Bristol Stool Scale Category 6 or 7) and AP ≤1 and not worse than baseline.j Endoscopic remission is defined as SES-CD Total Score ≤4 and at least a 2-point reductionversus baseline and no subscore >1 in any individual variable, based on central reading.k Corticosteroid-free is defined as patients who were corticosteroid-free from week 40 to week 52.

Bowel urgency remission

Bowel urgency remission was assessed during VIVID-1 with an urgency numeric rating scale (NRS)of 0 to 10. A greater proportion of patients with a baseline urgency NRS weekly average score ≥3treated with mirikizumab compared to placebo achieved clinical response by PRO at week 12 and anurgency NRS weekly average score of ≤ 2 at week 52 (33 % versus 11 %).

Table 5. Proportion of patients with Crohn’s disease meeting efficacy endpoints in VIVID -1 atweek 12

Endpoint Placebo Mirikizumab Treatmentn=199 900 mg Difference from

IV infusiona Placebobn=579 (99.5% CI)n % n %

Clinical response by PROc 103/199 52 % 409/579 71 % 19 %e (8 %, 30 %)

Clinical remission by CDAIg 50/199 25 % 218/579 38 % 12 %h (2 %, 23 %)

Endoscopic responsed 25/199 13 % 188/579 32 % 20 %e (11 %, 28 %)

Endoscopic remissionj 14/199 7 % 102/579 18 % 11 %h (4 %, 17 %)

Change from baseline in FACIT-fatigueh LS Mean SE LS Mean SE2.6 0.61 5.9 0.36 3.2f (1.2, pct. 5.2)

Abbreviations: FACIT-fatigue = Functional Assessment of Chronic Illness Therapy - fatigue;

LS Mean = Least Square Mean; SE = Standard Error; others see above table 4.a Weeks 0, 4, 8b see table 4. Also see footnote k.c, d, e, g, j see table 4f p-value <0.005h For change from baseline in FACIT-fatigue, the LS means and treatment difference were basedon ANCOVA model adjusted for baseline FACIT-fatigue and other covariates. At baseline, mean

FACIT-fatigue values were similar across treatment groups and ranged from 32.3-31.5.

Improvements in clinical remission by CDAI were observed as early as week 4 in a greaterproportion of patients treated with mirikizumab compared to placebo.

Reductions in abdominal pain were observed as early as week 4 and in stool frequency as early asweek 6 in patients treated with mirikizumab compared to placebo.

The efficacy and safety profile of mirikizumab was consistent across subgroups, i.e. age, gender,body weight, disease activity severity at baseline and region. The effect size may vary.

Active comparator arm

At week 52, mirikizumab demonstrated non-inferiority (pre-specified margin of -10%) toustekinumab on clinical remission by CDAI (mirikizumab 54 %; ustekinumab 48 %). Superiorityover ustekinumab in week 52 endoscopic response was not achieved (mirikizumab 48 %,ustekinumab 46 %).

Histologic outcome

Across all five intestinal segments 44 % of patients on mirikizumab achieved the composite endpointof clinical response by PRO at week 12 and histologic response at week 52 compared to 16 % ofpatients on placebo. Histologic response at week 52 was achieved by 58 % of patients compared to49% on ustekinumab.

At week 12, change in the Inflammatory Bowel Disease Questionnaire (IBDQ) score was 36.9 formirikizumab and 17.4 for placebo; IBDQ response and remission were achieved in 69 % and 52 %of mirikizumab-treated patients versus 45 % and 28 % in placebo patients respectively. Theseimprovements were maintained at week 52.

The European Medicines Agency has deferred the obligation to submit the results of studies with

Omvoh in one or more subsets of the paediatric population in the treatment of ulcerative colitis and

Crohn’s disease (see section 4.2 for information on paediatric use).

There was no apparent accumulation in serum mirikizumab concentration over time when givensubcutaneously every 4 weeks.

Exposure

Mean (coefficient of variation in %) Cmax and area under the curve (AUC) after induction dosing(300 mg every 4 weeks administered by intravenous infusion) in patients with ulcerative colitis were99.7 µg/mL (22.7 %) and 538 µg*day/mL (34.4 %), respectively. The mean (CV %) Cmax and AUCafter maintenance dosing (200 mg every 4 weeks by subcutaneous injection) were 10.1 µg/mL(52.1 %) and 160 µg*day/mL (57.6 %), respectively.

Mean (coefficient of variation in %) Cmax and area under the curve (AUC) after induction dosing(900 mg every 4 weeks administered by intravenous infusion) in patients with Crohn’s disease were332 µg/mL (20.6 %) and 1820 µg*day/mL (38.1 %), respectively. The mean (CV %) Cmax and AUCafter maintenance dosing (300 mg every 4 weeks by subcutaneous injection) were 13.6 µg/mL(48.1 %) and 220 µg*day/mL (55.9 %), respectively.

Following subcutaneous dosing of mirikizumab for ulcerative colitis, median (range) Tmax was 5(3.08-6.75) days post dose and geometric mean (CV%) absolute bioavailability was 44 % (34%).

Following subcutaneous dosing of mirikizumab for Crohn’s disease, median (range) Tmax was 5 (3to 6.83) days post dose and geometric mean (CV%) absolute bioavailability was 36.3% (31%).

Injection site location did not significantly influence absorption of mirikizumab.

The geometric mean total volume of distribution was 4.83 L (21 %) in patients with ulcerative colitisand 4.40 L (14 %) in patients with Crohn’s disease.

Mirikizumab is a humanised IgG4 monoclonal antibody and is expected to be degraded into smallpeptides and amino acids via catabolic pathways in the same manner as endogenous IgGs.

In the population PK analysis, geometric mean (CV %) clearance was 0.0229 L/hr (34 %) and thegeometric mean half-life is approximately 9.3 days (40 %) in patients with ulcerative colitis. Thegeometric mean (CV%) clearance was 0.0202 L/hr (38 %) and the geometric mean (CV %) half-lifeis also approximately 9.3 days (26 %) in patients with Crohn’s disease. Clearance is independent ofdose.

Dose proportionality

Mirikizumab exhibited linear pharmacokinetics with dose-proportional increase in exposure over adose range of 5 to 2 400 mg given as an intravenous infusion or over a dose range of 120 to 400 mggiven as a subcutaneous injection in patients with ulcerative colitis or Crohn’s disease or in healthyvolunteers.

Population pharmacokinetic analysis showed that age, sex, weight, or race/ethnicity did not have aclinically meaningful effect on the pharmacokinetics of mirikizumab (see also section 4.8,“immunogenicity”). Among the 1 362 subjects with ulcerative colitis exposed to mirikizumab in

Phase 2 and Phase 3 studies, 99 (7.3 %) patients were 65 years or older and 11 (0.8 %) patients were75 years or older.

Specific clinical pharmacology studies to evaluate the effects of renal impairment and hepaticimpairment on the pharmacokinetics of mirikizumab have not been conducted.

In patients with ulcerative colitis, population pharmacokinetic analysis showed that creatinineclearance (range of 36.2 to 291 mL/min) or total bilirubin (range of 1.5 to 29 µmol/L) did not affectmirikizumab pharmacokinetics.

In patients with Crohn’s disease, population pharmacokinetic analysis showed that creatinineclearance (range of 26.5 to 269 mL/min) or total bilirubin (range of 1.5 to 36 µmol/L) did not affectmirikizumab pharmacokinetics.

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeated dose toxicity, toxicity to reproduction and development.

Non-clinical studies have not been conducted to evaluate the carcinogenic or mutagenic potential ofmirikizumab.

No reproductive organ weight or histopathology effects were observed in sexually maturecynomolgus monkeys that received mirikizumab once weekly for 26 weeks, at a dose of 100 mg/kg(at least 20 times the human maintenance dose).

Sodium citrate dihydrate (E 331)

Citric acid, anhydrous (E 330)

Sodium chloride

Polysorbate 80 (E 433)

Water for injections

This medicinal product must not be mixed with other medicinal products except those mentioned insection 6.6.

Omvoh should not be administered concomitantly in the same intravenous line with other medicinalproducts.

2 years.

Chemical and physical in-use stability has been demonstrated for diluted infusion solution preparedwith sodium chloride 9 mg/mL (0.9 %) solution for 96 hours at 2 °C to 8 °C of which not more than10 hours are permitted at non-refrigerated temperatures not to exceed 25 ºC, starting from the time ofvial puncture.

Chemical and physical in-use stability has been demonstrated for diluted infusion solution preparedwith 5 % glucose for 48 hours at 2 °C to 8 °C of which not more than 5 hours are permitted at non-refrigerated temperatures not to exceed 25 °C, starting from the time of vial puncture.

From a microbiological point of view, the product should be used immediately. If not usedimmediately, in-use storage times and conditions prior to use are the responsibility of the user andwould normally not be longer than 24 hours at 2 to 8 °C, unless dilution has taken place in controlledand validated aseptic conditions.

Keep the diluted solution away from direct heat or light.

Do not freeze the diluted solution.

Store in a refrigerator (2 ºC - 8 ºC).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

15 mL concentrate in a type I clear glass vial with a chlorobutyl rubber stopper, an aluminium sealand polypropylene flip top.

Pack sizes of 1 vial and 3 vials.

Not all pack sizes may be marketed.

Do not use Omvoh that has been frozen.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Dilution prior to intravenous infusion1. Each vial is for single use only.2. Prepare the infusion solution using aseptic technique to ensure the sterility of the preparedsolution.3. Inspect the content of the vial. The concentrate should be clear, colourless to slightly yellowand free of visible particles. Otherwise, it should be discarded.4. Prepare the infusion bag for treatment of either ulcerative colitis or Crohn’s disease asspecified below. Note that there are unique instructions and volumes specified for eachindication.

Ulcerative colitis: one 15 mL vial (300 mg)

Withdraw 15 mL of the mirikizumab vial (300 mg) using an appropriately sized needle (18 to21 gauge is recommended) and transfer to the infusion bag. If administered for the treatmentof ulcerative colitis, the concentrate should be diluted only in infusion bags (bag size rangingfrom 50 - 250 mL) containing either sodium chloride 9 mg/mL (0.9 %) solution for injectionor 5 % glucose solution for injection. The final concentration after dilution is approximately1.1 mg/mL to approximately 4.6 mg/mL.

Crohn’s disease: three 15 mL vials; total volume = 45 mL (900 mg)

First, withdraw and discard 45 mL of diluent from the infusion bag. Next, withdraw 15 mLfrom each of the three mirikizumab vials (900 mg) and transfer to the infusion bag, using anappropriately sized syringe and needle (18 to 21 gauge is recommended). If administered forthe treatment of Crohn’s disease, the concentrate should be diluted only in infusion bags (bagsize ranging from 100-250 mL) containing either sodium chloride 9 mg/mL (0.9 %) solutionfor injection or 5 % glucose solution for injection.

The final concentration after dilution is approximately 3.6 mg/mL to approximately 9 mg/mL.

5. Gently invert the infusion bag to mix. Do not shake the prepared bag.

Eli Lilly Nederland B.V.

Papendorpseweg 833528 BJ Utrecht

The Netherlands

EU/1/23/1736/001

EU/1/23/1736/011

Date of first authorisation: 26 May 2023

Detailed information on this medicinal product is available on the website of the European

Medicines Agency https://www.ema.europa.eu.