ANDEMBRY Solution for injection Ref.[114884] Active ingredients: Garadacimab

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 have not been observed but may theoretically occur. In case of severe hypersensitivity reactions, administration of garadacimab should be discontinued, and appropriate treatment instituted.

General

ANDEMBRY is not intended for treatment of acute HAE attacks. In case of breakthrough HAE attack, individualized treatment should be initiated with an approved rescue medicinal product.

There are limited data available on the use of garadacimab in HAE patients with nC1-INH (see section 5.1).

Some subcategories of nC1-INH HAE may not respond to treatment with garadacimab due to alternative pathways that do not include FXII activation. It is recommended to perform genetic testing, if available, according to the current HAE guidelines and to discontinue the treatment if clinical response is not observed (see sections 4.2 and 5.1).

Interference with coagulation test

ANDEMBRY can prolong activated partial thromboplastin time (aPTT) due to an interaction of garadacimab with the aPTT assay. The extent of aPTT prolongation could be variable depending on drug exposure as well as additional parameters, such as natural variation in FXII levels, and other coagulation factors. The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of FXII in the contact system, therefore inhibition of plasma FXIIa by ANDEMBRY can prolong aPTT in this assay.

Excipients

This medicinal product contains 19.3 mg of proline in each pre-filled syringe/pen which is equivalent to 16.1 mg/mL. Proline may be harmful for patients with hyperprolinaemia, a rare genetic disorder in which proline builds up in the body.

This medicinal product contains 0.24 mg of polysorbate 80 in each pre-filled syringe/pen which is equivalent to 0.2 mg/mL. Polysorbates may cause allergic reactions.

No dedicated drug-drug interaction studies have been conducted in humans. Garadacimab has only been studied as a monotherapy and not in combination with other products indicated for long-term prophylaxis of HAE. The use of analgesic, antibacterial, antihistamine, anti-inflammatory and anti-rheumatic medications had no effect on the PK of garadacimab. For breakthrough HAE attacks, use of rescue medications such as plasma-derived and recombinant C1-INH or icatibant had no effect on the PK of garadacimab.

Pregnancy

There are no or limited amount of data from the use of garadacimab in pregnant women. Monoclonal antibodies such as garadacimab are transported across the placenta mainly during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. A pre- and postnatal development study conducted in pregnant rabbits revealed no evidence of harm to the developing fetus. (see section 5.3). As a precautionary measure, it is preferable to avoid the use of garadacimab during pregnancy.

Breast-feeding

It is unknown whether garadacimab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, and decrease to low concentrations soon afterwards. Consequently, transfer of IgG antibodies to the newborns through milk may happen during the first few days. In this short period, a risk to the breast-fed child cannot be excluded. Afterwards, garadacimab could be used during breast-feeding if clinically needed.

Fertility

Effect on fertility has not been evaluated in humans. Garadacimab had no effect on male or female fertility in rabbits (see section 5.3).

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

Summary of the safety profile

The most commonly observed adverse reactions associated with ANDEMBRY were injection site reactions (ISR) including injection site erythema, injection site bruising, injection site pruritus and injection site urticaria, headache and abdominal pain.

Tabulated list of adverse reactions

Table 1 summarises adverse reactions observed in the VANGUARD pivotal trial, which included 39 subjects with HAE who received at least 1 dose of ANDEMBRY.

The frequency of adverse reactions listed in Table 1 is defined using 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 drug reactions (ADRs) obtained from clinical studies with ANDEMBRY:

^* Injection site reactions include, erythema, bruising, pruritus, and injection site urticaria

Paediatric population

The safety of ANDEMBRY was evaluated in a subgroup of 11 subjects aged 12 to <18 years old. No difference from the overall safety profile was seen between adults and children.

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.

Not applicable.