Lanadelumab

Lanadelumab is a fully human monoclonal antibody (IgG1/κ-light chain). Lanadelumab inhibits the proteolytic activity of active plasma kallikrein. Increased plasma kallikrein activity leads to angioedema attacks in patients with HAE through proteolysis of high molecular weight kininogen (HMWK), which produces cleaved HMWK (cHMWK) and bradykinin. Lanadelumab provides sustained control of plasma kallikrein activity and therefore limits bradykinin formation in patients with hereditary angioedema (HAE).

After s.c. administration of lanadelumab 150 mg every 4 weeks, 300 mg every 4 weeks, or 300 mg every 2 weeks in study participants with HAE, a concentration-dependent inhibition of plasma kallikrein, measured as a reduction in cHMWK levels, was observed.

To date, there is no or only very limited experience with the use of lanadelumab in pregnant women. Animal studies did not reveal any evidence of direct or indirect adverse health effects with regard to reproductive or developmental toxicity (see section 5.3). For precautionary reasons, use of lanadelumab during pregnancy should be avoided.

The most common (52.4%) adverse reactions observed in association with TAKHZYRO® were injection site reactions (ISRs), including injection site pain, injection site erythema, and injection site bruising. Of these ISRs, 97% were mild, and 90% resolved within 1 day of onset, with a median duration of 6 minutes. Hypersensitivity reactions (mild and moderate pruritus, discomfort, and tingling of the tongue) were observed (1.2%).

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

TAKHZYRO® 300 mg solution for injection in a vial 2 years The injection should be used within 2 hours after preparation of the application syringe. If not used immediately after preparation, the syringe may be stored in the refrigerator (2 °C to 8 °C) protected from light and used within 8 hours.