Lanadelumab

As expected, concomitant use of the rescue medication C1 esterase inhibitor results in an additive effect on lanadelumab-cHMWK response based on the mechanism of action (MOA) of lanadelumab and C1 esterase inhibitor.

Lanadelumab can increase activated partial thromboplastin time (aPTT) due to an interaction of lanadelumab with the aPTT assay. The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of plasma kallikrein in the contact system. Inhibition of plasma kallikrein by lanadelumab can increase aPTT in this assay. None of the increases in aPTT in patients treated with lanadelumab were associated with abnormal bleeding adverse events. There were no differences in international normalised ratio (INR) between treatment groups.

There are no or limited data from the use of lanadelumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive or developmental toxicity. As a precautionary measure, it is preferable to avoid the use of lanadelumab during pregnancy.

It is unknown whether lanadelumab 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 child cannot be excluded during this short period. Afterwards, lanadelumab could be used during breast-feeding if clinically needed.

Fertility

Lanadelumab’s effect on fertility has not been evaluated in humans. Lanadelumab had no effect on male or female fertility in cynomolgus monkeys.

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

Summary of the safety profile

The most commonly (52.4%) observed adverse reaction associated with lanadelumab was injection site reactions (ISR) including injection site pain, injection site erythema and injection site bruising. Of these ISRs, 97% were of mild intensity, 90% resolved within 1 day after onset with a median duration of 6 minutes.

Hypersensitivity reaction (mild and moderate pruritus, discomfort and tingling of tongue) was observed (1.2%).

Tabulated list of adverse reactions

The table below summarises adverse reactions observed in the HELP study that included 84 subjects with HAE, who received at least one dose of lanadelumab.

The frequency of adverse reactions listed in the 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 reactions reported with lanadelumab:

^* Hypersensitivity includes: pruritus, discomfort and tingling of tongue.
^** Injection site reactions include: pain, erythema, bruising, discomfort, haematoma, haemorrhage, pruritus, swelling, induration, paraesthesia, reaction, warmth, oedema and rash.

Safety data available from the HELP study extension are consistent with the safety data from the HELP study (described in the table above).

Paediatric population

The safety of lanadelumab 300 mg/2 ml was evaluated in a subgroup of 23 subjects 12 to less than 18 years of age in the HELP and HELP study extension. In the SPRING study, safety of lanadelumab was also evaluated at 150 mg/1 ml in 21 subjects 2 to less than 12 years of age. No subject below the age of 3.5 years was receiving lanadelumab in the study. No new adverse reactions were identified. Safety and tolerability results for paediatric subjects were consistent with overall study results for all subjects.