Garadacimab

Garadacimab 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 garadacimab can prolong aPTT in this assay.

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

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.

Garadacimab 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 garadacimab 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

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

The frequency of adverse reactions listed in the following table 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).

Adverse drug reactions (ADRs) obtained from clinical studies with garadacimab:

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

Paediatric population

The safety of garadacimab 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.