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), resulting in cleaved HMWK (cHMWK) and bradykinin. Lanadelumab provides sustained control of plasma kallikrein activity and therefore limits bradykinin formation in patients with hereditary angioedema (HAE).

The monoclonal antibody lanadelumab has been approved in Europe since 2015 as a long-term prophylaxis to prevent attacks in hereditary angioedema.

In a multicenter double-blind phase Ib study in patients with hereditary angioedema (absence or dysfunction of the C1 inhibitor - congenital due to heterozygous mutation of the SERPING1 gene or acquired due to autoantibodies against the C1 esterase inhibitor), a reduction of angioedema attacks by 80-100% was achieved compared to placebo. The clinical effects appear to be higher than those of the C1 inhibitor plasma preparation (Cinryze®). In this Phase 1b study, no serious adverse events or discontinuations due to adverse events were observed at any dose studied.

Efficacy analyses in 37 patients with at least 2 attacks in the 3 months prior to study enrollment showed that from Day 8 to Day 50, administration of two doses of lanadelumab (300 or 400 mg) 14 days apart reduced attacks by 100% and 88%, respectively, compared to placebo. In addition, all subjects in the 300 mg group and 82% in the 400 mg group were free of attacks, compared with 27% in the placebo group.

A Phase 3 study evaluating the safety and efficacy of lanadelumab as a long-acting prophylactic treatment for hereditary angioedema (HAE) is currently underway. The results remain to be seen.

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%).

TAKHZYRO 300 mg® Solution for InjectionTAKHZYRO
300 mg® Solution for Injection in a Prefilled Syringe

Used in patients 12 years of age and older for routine prophylaxis of recurrent attacks of hereditary angioedema (HAE).

Kallikreine is a group of proteolytic enzymes from which plasma kinines are derived. Five different types are distinguished, which represent a physiological regulatory system and control a number of physiological functions. Kallikrein is involved in intrinsic plasma coagulation, the fibrinolytic system, the renin-angiotensin system and the alternative complement system.

1. Banerji A et al (2017) Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. N Engl J Med 376:717-728.
2. Chyung Y et al (2014) A phase 1 study investigating DX-2930 in healthy subjects. Ann Allergy Asthma Immunol 113:460-466 Kenniston JA et al. (2014) Inhibition of plasma kallikrein by a highly specific active site blocking antibody. J Biol Chem 289:23596-2608.
3. Wedi B (2017) Lanadelumab. dermatologist 68: 585-587