Lanadelumab

Hereditary angioedema (HEA) is an autosomal dominant disorder resulting from the presence of C1 deficiency. This condition manifests as attacks of subcutaneous or submucosal edema in the face, larynx, GI tract, limbs or genitalia, with laryngeal edema being the most serious due to the potential to compromise the airways. Attacks may be accompanied by pain and considerable dysfunction.

Lanadelumab is a plasma kallikrein inhibitor. This enzyme works by cleaving high molecular weight kininogen to generate the pro-inflammatory peptide bradykinin, a potent vasodilator. Because the activity of plasma kallikrein is regulated by C1 esterase inhibitor, patients deficient in C1 esterase inhibitor may be at risk of excessive production of bradykinin leading to serious angioedema. Lanadelumab occludes the proteolytic active site of plasma kallikrein, preventing the cleavage of kininogen to bradykinin. It is a selective inhibitor and does not bind to prekallikrein or inhibit other serine proteases.