EXDENSUR Solution for injection Ref.[116332] Active ingredients: Depemokimab

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

Hypersensitivity reactions, such as anaphylaxis and angioedema, may occur following administration of depemokimab (see section 4.8). These reactions may occur within hours of administration, but some may have a delayed onset (i.e., days). In the event of a hypersensitivity reaction, appropriate treatment as clinically indicated, is recommended. Upon re-administration of depemokimab monitoring to detect signs of recurring hypersensitivity reactions is recommended. In case of a severe or recurring hypersensitivity reaction, permanent discontinuation of depemokimab should be considered.

Acute asthma exacerbations

Depemokimab must not be used to treat acute asthma symptoms or acute exacerbations.

Asthma-related adverse symptoms or exacerbations may occur during treatment with depemokimab. It is recommended that patients be instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with depemokimab.

Corticosteroids

Abrupt discontinuation of background treatments (including systemic and inhaled corticosteroids) after initiation of depemokimab therapy is not recommended. Reductions in the doses of background treatments, if appropriate, must be gradual and performed under the supervision of a physician.

Parasitic (helminth) infections

Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-existing helminth infections were excluded from the clinical programme. Patients with pre-existing helminth infections should be treated for their infection prior to depemokimab therapy. If patients become infected while receiving treatment with depemokimab and do not respond to anti-helminth treatment, delaying administration of the next depemokimab dose until the infection resolves should be considered.

Excipients with known effect

Polysorbates

This medicinal product contains 0.2 mg of polysorbate 80 per 100 mg dose (see section 2). Polysorbates may cause allergic reactions.

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose, that is to say essentially "sodium-free".

No interaction studies have been performed. The potential for drug-drug interactions is considered to be low as depemokimab is catabolised by ubiquitous proteolytic enzymes, not restricted to hepatic tissue. The risk of drug disease interaction due to an indirect effect on gene expression of cytochrome P450 (CYP450) or transporters is also considered to be low since the specific target for depemokimab is the cytokine interleukin-5 (IL-5).

Pregnancy

There are no or limited amount of data from the use of depemokimab in pregnant women. Animal studies targeting IL-5 signalling pathways do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Monoclonal antibodies, such as depemokimab, are expected to be transported across the placenta in a linear fashion as pregnancy progresses.

As a precautionary measure, it is preferable to avoid the use of EXDENSUR during pregnancy.

Breast-feeding

It is unknown whether depemokimab 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. Afterwards, EXDENSUR could be used during breast-feeding if clinically needed.

Fertility

There are no fertility data in humans. Animal studies have shown no adverse effects of anti-IL-5 treatment on fertility (see section 5.3).

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

Summary of the safety profile

The most common adverse reactions reported with depemokimab are local injection site reactions (2%).

Tabulated list of adverse reactions

Adverse reactions reported during clinical trials are presented in the table below (Table 1). Frequencies are defined as 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) and very rare (<1/10 000). Within each frequency grouping, where relevant, adverse reactions are presented in order of decreasing seriousness.

Table 1. Adverse reactions:

Description of selected adverse reactions

Systemic reactions (allergic)

Hypersensitivity reactions, such as anaphylaxis and angioedema, have been reported with other monoclonal antibodies that target IL-5 or its receptor. These reactions may occur based on the experience with the class (see section 4.4).

Systemic reactions (non-allergic)

Administration-related non-allergic reactions (e.g., headache, fatigue, rash) were reported in 1% of patients receiving depemokimab in the entire clinical development programme. In the 52-week placebo-controlled studies in asthma and CRSwNP, systemic non-allergic reactions were reported in <1% of patients receiving depemokimab.

Systemic reactions (non-allergic) reported with depemokimab were non-serious and were either mild or moderate in intensity. The majority of events were transient: 88% of events resolved ≤7 days from onset whereas, 67% of events resolved ≤2 days from their onset.

Local injection site reactions

Local injection site reactions (e.g., pain, erythema, swelling, itching) were reported in 2% of patients receiving depemokimab in the entire clinical development programme. The reactions reported with depemokimab were non-serious, mild in intensity and were transient (79% resolved in ≤7 days, with most events (56%) resolving in ≤2 days from their onset).

In the placebo-controlled studies in asthma and CRSwNP, local injection site reactions were reported in 1% of patients receiving depemokimab compared to <1% of patients who received placebo.

Paediatric population

Fifteen adolescents (aged 12-17) received depemokimab in two placebo-controlled studies for asthma (SWIFT-1 and SWIFT-2) of 52 weeks duration. The safety profile was generally similar to that seen in adults. No additional adverse reactions were identified.

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.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.