OMVOH Concentrate for solution for infusion Ref.[50981] Active ingredients: Mirikizumab

Traceability

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

Hypersensitivity reactions

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, including anaphylaxis, occurs, mirikizumab must be discontinued immediately and appropriate therapy must be initiated.

Infections

Mirikizumab may increase the risk of severe infection (see section 4.8). Treatment with mirikizumab should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated (see section 4.3). The risks and benefits of treatment should be considered prior to initiating use of mirikizumab in patients with a chronic infection or a history of recurrent infection. Patients should be instructed to seek medical advice if signs or symptoms of clinically important acute or chronic infection occur. If a serious infection develops, discontinuation of 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. Patients receiving mirikizumab should be monitored for signs and symptoms of active TB during and after treatment. Anti-TB therapy should be considered prior to initiating treatment in patients with a past history 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 in patients receiving mirikizumab in clinical trials. Liver enzymes and bilirubin should be evaluated at baseline and monthly during induction (including extended induction period, if applicable). Thereafter, liver enzymes and bilirubin should be monitored (every 1-4 months) according to standard practice for patient management and as clinically indicated. If increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) are observed and drug-induced liver injury is suspected, mirikizumab must be discontinued until this diagnosis is excluded.

Immunisations

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

Excipients with known effect

Sodium

Ulcerative colitis:

This medicinal product contains 60 mg sodium per 300 mg dose, equivalent to 3% of the WHO recommended 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 sodium contributed by the sodium chloride diluent will range from 177 mg (for a 50 mL bag) to 885 mg (for a 250 mL bag), equivalent to 9-44% of the WHO recommended maximum daily intake. This is in addition to the amount contributed by the medicinal product.

Crohn’s disease:

This medicinal product contains 180 mg sodium per 900 mg dose, equivalent to 9% of the WHO recommended 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 sodium contributed 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 is in 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 to 7.5 mg for the induction dose to treat ulcerative colitis and equivalent to 22.5 mg for the induction dose 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 influence the safety of mirikizumab.

Population pharmacokinetic data analyses indicated that the clearance of mirikizumab was not impacted by concomitant administration of 5-ASAs (5-aminosalicylic acid), corticosteroids or oral immunomodulators (azathioprine, 6-mercaptopurine, thioguanine, and methotrexate).

Women of childbearing potential

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

Pregnancy

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

Breast-feeding

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

Fertility

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.

Summary of the safety profile

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

Tabulated list of adverse reactions

Adverse reactions from clinical studies (Table 1) are listed by MedDRA system organ class. The frequency 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); very rare (<1/10 000).

Table 1. Adverse reactions:

^a Includes: acute sinusitis, COVID-19, nasopharyngitis, oropharyngeal discomfort, oropharyngeal pain, pharyngitis, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection, and viral upper respiratory 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 administered as subcutaneous injection.
^d Reported during mirikizumab induction therapy where mirikizumab treatment is administered as intravenous infusion.

Description of selected adverse reactions

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 frequent reactions were injection site pain, injection site reaction and injection site erythema. These symptoms were reported as non-serious, mild and transient in nature.

The results described above were obtained with the original formulation of Omvoh. In a double blind, 2-arm, randomised, single-dose, parallel design study in 60 healthy subjects comparing 200 mg mirikizumab (2 injections of 100 mg in a pre-filled syringe) of the original formulation with the revised formulation statistically significantly lower VAS pain scores were obtained with the revised (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. AST increased was reported by 0.4% mirikizumab-treated patients. All adverse reactions were reported as mild to moderate in severity and non-serious.

Overall mirikizumab treatment periods in the ulcerative colitis and Crohn’s disease clinical development program (including the placebo-controlled and open label induction and maintenance periods), 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 been noted with and without concomitant elevations in total bilirubin.

Immunogenicity

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

In the Crohn’s disease study, 12.7% of mirikizumab-treated patients with 12 months of treatment developed anti-drug antibodies, most of which were of low titer and tested positive for neutralising activity. There was no identified clinically significant effect of anti-drug antibodies on pharmacokinetics 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 of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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

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