KAVIGALE Solution for injection/infusion Ref.[114761] Active ingredients: Sipavibart

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.

Antiviral resistance

Sipavibart was designed to be effective against early omicron strains, with pseudovirus neutralisation IC₅₀ values ranging from 3.6 ng/ml (XBB.1 variant) to 25.0 ng/ml (BA.2.75 variant). The extent and duration of protective efficacy against viruses with moderately increased IC₅₀ (e.g. JN.1, IC₅₀ 83.1 ng/ml) is reduced and the clinical relevance of any prophylactic effect unclear. Due to the absence of in vitro neutralising activity, sipavibart is not anticipated to provide any protection against symptomatic COVID-19 due to viral variants containing F456L mutations in the spike protein (see section 5.1).

Decisions regarding the use of sipavibart for the prevention of COVID-19 should take into consideration what is known about the characteristics of the circulating SARS-CoV-2 viral variants, including geographical prevalence. The in vitro neutralisation activity of sipavibart against SARS-CoV-2 viral variants is shown in Table 2 (see section 5.1).

Patients who receive sipavibart should be informed of the potential for breakthrough infections to occur. If signs or symptoms of COVID-19 occur (the most common symptoms include fever, chills, sore throat, cough, tiredness, and new loss of taste or smell; the most serious symptoms include difficulty breathing or shortness of breath, loss of speech or mobility, or confusion and chest pain), advise individuals to promptly seek medical attention.

Hypersensitivity including anaphylaxis

Serious hypersensitivity reactions, including anaphylaxis, have been observed with human immunoglobulin G1 (IgG1) monoclonal antibodies. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration, and initiate appropriate medicinal products and/or supportive therapy.

Infusion-related reactions

IRRs were observed in clinical trials with intravenous administration of sipavibart and were mild in severity (see section 4.8). If signs and symptoms of an IRR occur, the infusion should be interrupted, slowed, or stopped and appropriate medicinal products and/or supportive therapy should be administered.

Clinically significant bleeding disorders

As with any other intramuscular injections, sipavibart should be given with caution to patients with thrombocytopenia or any coagulation disorder.

COVID-19 vaccines

Pre-exposure prophylaxis with sipavibart is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended.

Excipient with known effect

This medicinal product contains 0.8 mg of polysorbate 80 in each vial. Polysorbates may cause allergic reactions.

No interaction studies have been performed.

Sipavibart is not expected to be renally excreted or metabolised by cytochrome P450 enzymes (see section 5.2). Therefore, interactions with concomitant medicinal products that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Pregnancy

There are no data on the use of sipavibart in pregnant women.

Non-clinical reproductive toxicity studies have not been performed with sipavibart. In a tissue cross reactivity study with sipavibart, no binding was detected to human foetal tissue or reproductive tissues.

Human IgG1 antibodies are known to cross the placenta barrier; therefore, sipavibart has the potential to be transferred from the mother to the developing foetus. It is unknown whether the potential placental transfer of sipavibart provides any treatment benefit or risk to the developing foetus.

Sipavibart should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the foetus.

Breast-feeding

It is unknown whether sipavibart is excreted in human milk. In humans, excretion of IgG antibodies in milk occurs during the first few days after birth, decreasing to low concentrations soon afterwards. Consequently, a risk to the breast-fed infant cannot be excluded during this short period. Afterwards, sipavibart could be used during breast-feeding if clinically needed.

Fertility

There are no data on the effects of sipavibart on human fertility.

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

Summary of the safety profile

In patients receiving sipavibart by intramuscular injection, the most common adverse reaction is injection site reaction (4.1%). In patients receiving sipavibart by intravenous infusion, the most common adverse reactions are infusion site reactions (1.9%) and infusion-related reactions (1.9%).

Tabulated list of adverse reactions

Table 1 presents the adverse reactions identified from the clinical studies.

The adverse reactions in Table 1 are listed by MedDRA system organ class (SOC). Within each SOC, preferred terms are arranged by decreasing frequency, and then by decreasing seriousness. Frequencies of occurrence of adverse reactions 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); very rare (<1/10 000), and not known (cannot be estimated from the available data).

Table 1. Tabulated list of adverse reactions:

^a Including the following preferred terms: pruritus, erythema, hypersensitivity, urticaria, dermatitis allergic, and drug eruption.
^b Including the following preferred terms: injection site pain, injection site bruising, injection site erythema, injection site haemorrhage, injection site swelling, injection site haematoma, injection site pruritus, injection site paraesthesia, injection site reaction, injection site rash, injection site discolouration, and injection site warmth.
^c Including the following preferred terms: infusion site bruising, infusion site pain, infusion site pruritus, infusion site erythema, infusion site extravasation, and infusion site swelling.
^d Including the following symptoms: nausea, arthralgia, headache, pyrexia, chills, dyspepsia, pain, hypotension, facial flushing, coughing, chest discomfort, dizziness, and shortness of breath.

Description of selected adverse reactions

Hypersensitivity

Hypersensitivity reactions occurred within 14 days post-dose, were mild to moderate in severity, and most resolved within a few days.

Injection site reactions

Injection site reactions occurred within 7 days post-dose, were mild in severity, and most resolved within a few days.

Infusion site reactions

Infusion site reactions occurred within 7 days post-dose, were mild to moderate in severity, and resolved within a few days.

Infusion-related reactions

Infusion-related reactions occurred during or on the same day of infusion, were mild to moderate in severity, and resolved within a few days.

Paediatric population

There are limited safety data available for paediatric patients ≥12 years to <18 years of age (n=8). No data are available for paediatric patients <12 years of age. The safety profile in paediatric participants ≥12 years of age was similar to the safety profile in adults.

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 except those mentioned in section 6.6.