Lanadelumab

Lanadelumab (SHP643) is a human IgG1 monoclonal antibody against plasma kallikrein (pKal) with an Ki value of 0.12 nM. Lanadelumab inhibits both free and HMWK (high molecular weight kininogen)-bound pKal. Lanadelumab has the potential for the research of hereditary angioedema.

Lanadelumab (0-1000 nM) inhibits pKal proteolytic activity of single-chain HMWK (its endogenous protein substrate), and addition of Lanadelumab to pKal samples in vitro preventes the proteolysis of HMWK and the consequent release of bradykinin with an IC₅₀ value of 1.3 nM^[2].

Lanadelumab (20 mg/kg; i.v. or s.c.) shows a long half-life of about 12.5 days and blocks high molecular weight kininogen proteolysis in activated plasma in a dose- and time-dependent manner in cynomolgus monkeys^[2].
Lanadelumab (1, 30 mg/kg; s.c.) inhibits carrageenan-induced paw edema in the Male Sprague-Dawley rats ^[2].

References:
[1]. Riedl MA, et al. Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks. Allergy. 2020 Nov;75(11):2879-2887.
[2]. Kenniston JA, et al. Inhibition of plasma kallikrein by a highly specific active site blocking antibody. J Biol Chem. 2014 Aug 22;289(34):23596-608.