BRIEF SUMMARY

MIRIKIZUMAB- (Oct 2023)

Indn-    to treat ulcerative colitis        

Comp-    Intravenous Infusion- • The recommended induction dosage is 300 mg administered by intravenous infusion over at least 30 minutes at Weeks 0, 4, and 8.

 • The recommended maintenance dosage is 200 mg administered by subcutaneous injection (given as two consecutive injections of 100 mg each) at Week 12, and every 4 weeks thereafter.

ADR-   Most common adverse reactions (=2%) are:                                                           • Induction: upper respiratory tract infections and arthralgia.                                               • Maintenance: upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

CI-    • Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis and infusion-related reactions, have been reported. If a severe hypersensitivity reaction occurs, discontinue and initiate appropriate treatment.

 • Infections: OMVOH may increase the risk of infection. Do not initiate treatment with OMVOH in patients with a clinically important active infection until the infection resolves or is adequately treate

Pat Inform-

Hypersensitivity Reactions-                                                                                        Advise patients to discontinue OMVOH and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions

Infections-                                                                                                                           Advise patients that OMVOH may lower the ability of their immune system to fight infections and to conta

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 45

Name-          OMVOH

Active ingedient-       Mirikzumab- mrkz                 

Indication              to treat ulcerative colitis                                                                             

Date  of approval       10/26/2023 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                                OMVOH safely and effectively.

See full prescribing information for OMVOH. OMVOH (mirikizumab-mrkz) injection, for intravenous or subcutaneous use

Initial U.S. Approval: 2023-

 INDICATIONS AND USAGE-

OMVOHTM is an interleukin-23 antagonist indicated for the treatment of moderately to severely active ulcerative colitis in adults

ADVERSE REACTIONS-

 Most common adverse reactions (=2%) are:

• Induction: upper respiratory tract infections and arthralgia.

 • Maintenance: upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection. 

 CONTRAINDICATIONS-

 History of serious hypersensitivity reaction to mirikizumab-mrkz or any of the excipients.

WARNINGS AND PRECAUTIONS-

 • Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis and infusion-related reactions, have been reported. If a severe hypersensitivity reaction occurs, discontinue and initiate appropriate treatment.

 • Infections: OMVOH may increase the risk of infection. Do not initiate treatment with OMVOH in patients with a clinically important active infection until the infection resolves or is adequately treated. If a serious infection develops, do not administer OMVOH until the infection resolves.

 • Tuberculosis: Do not administer OMVOH to patients with active TB infection. Monitor patients receiving OMVOH for signs and symptoms of active TB during and after treatment.

 • Hepatotoxicity: Drug-induced liver injury has been reported. Monitor liver enzymes and bilirubin levels at baseline and for at least 24 weeks of treatment and thereafter according to routine patient management. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded.

 • Immunizations: Avoid use of live vaccines.

DOSAGE AND ADMINISTRATION-

 Prior to Treatment Initiation

• Evaluate patients for tuberculosis (TB) infection.

 • Obtain liver enzymes and bilirubin levels.

 • Complete all age-appropriate vaccinations according to current immunization guidelines.

 Recommended Dosage

• The recommended induction dosage is 300 mg administered by intravenous infusion over at least 30 minutes at Weeks 0, 4, and 8.

 • The recommended maintenance dosage is 200 mg administered by subcutaneous injection (given as two consecutive injections of 100 mg each) at Week 12, and every 4 weeks thereafter.

 Preparation and Administration

• See the full prescribing information for preparation, administration and storage information for intravenous infusion and subcutaneous injection.

DOSAGE FORMS AND STRENGTHS-

 Intravenous Infusion

 • Injection: 300 mg/15 mL (20 mg/mL) solution in a single-dose vial

PATIENT COUNSELING INFORMATION-

 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

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

Tuberculosis-                                                                                                             Advise patients to contact their healthcare provider if they experience symptoms suggestive of TB (e.g., unexplained fever, cough, or difficulty breathing)

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)].

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 

 Pregnancy-                                                                                                                     Advise patients who are exposed to OMVOH during pregnancy to contact Eli Lilly and Company

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.

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

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                            Mirikizumab-mrkz is a humanized IgG4 monoclonal antibody that selectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is involved in mucosal inflammation and affects the differentiation, expansion, and survival of T cell subsets, and innate immune cell subsets, which represent sources of pro-inflammatory cytokines.

2. Pharmacodynamics-                                                                                                    In both study UC-1 (induction) and study UC-2 (maintenance), a positive relationship was observed between mirikizumabmrkz average concentration and rates of clinical remission and clinical response 

3. Pharmacokinetics-

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.

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Absorption-                                                                                                                   Following subcutaneous dosing of OMVOH, median (range) Tmax 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.

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).

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.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Pregnancy-                                                                                        Exposure Registry Reference ID: 5267575 6 There will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to OMVOH during pregnancy.

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.

2 Lactation Risk Summary There are no data on the presence of mirikizumab-mrkz in human milk, the effects on the breastfed infant, or the effects on milk production.

3 Pediatric Use The safety and effectiveness of OMVOH have not been established in pediatric patients. Reference ID: 5267575 7

4 Geriatric Use 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.