TAKHZYRO Solution for injection Ref.[7637] Active ingredients: Lanadelumab

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 been observed. In case of a severe hypersensitivity reaction, administration of TAKHZYRO must be stopped immediately and appropriate treatment must be initiated.

General

TAKHZYRO is not intended for treatment of acute HAE attacks. In case of a breakthrough HAE attack, individualized treatment should be initiated with an approved rescue medication.

There are no available clinical data on the use of lanadelumab in HAE patients with normal C1-INH activity.

Interference with coagulation test

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 TAKHZYRO were associated with abnormal bleeding adverse events. There were no differences in international normalised ratio (INR) between treatment groups.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

No dedicated drug-drug interaction studies have been conducted. Based on the characteristics of lanadelumab, no pharmacokinetic interactions with co-administered medicinal products is expected.

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 (see section 5.1).

Pregnancy

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 (see section 5.3). As a precautionary measure, it is preferable to avoid the use of lanadelumab during pregnancy.

Breast-feeding

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 (see section 5.3).

TAKHZYRO has negligible influence on the ability to drive or use machines.

Summary of the safety profile

The most commonly (52.4%) observed adverse reaction associated with TAKHZYRO 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%), see section 4.4.

Tabulated list of adverse reactions

Table 1 summarises adverse reactions observed in the HELP study that included 84 subjects with HAE, who received at least one dose of TAKHZYRO.

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 reactions reported with lanadelumab:

Immune system disorders

Common: Hypersensitivity*

Nervous system disorders

Common: Dizziness

Skin and subcutaneous tissue disorders

Common: Rash maculo-papular

Musculoskeletal and connective tissue disorders

Common: Myalgia

General disorders and administration site conditions

Very common: Injection site reactions**

Investigations

Common: Alanine aminotransferase increased, Aspartate aminotransferase increased

* 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.

Paediatric population

The safety of TAKHZYRO was evaluated in a subgroup of 23 subjects aged 12 to <18 years old. Results of the subgroup analysis were consistent with overall study results for all subjects.

Immunogenicity

Treatment with lanadelumab has been associated with development of treatment emergent anti-drug antibodies (ADA) in 11.9% (10/84) of subjects. All antibody titres were low. The ADA response was transient in 20% (2/10) of ADA positive subjects. 2.4% (2/84) of lanadelumab-treated subjects tested positive for neutralizing antibodies.

The development of ADA including neutralising antibodies against TAKHZYRO did not appear to adversely affect the pharmacokinetic (PK) and pharmacodynamics (PD) profiles or clinical response.

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.