Hereditary angioedema (HAE) with
C1 esterase inhibitor (C1-INH) deficiency (C1-INH-HAE) is a
rare disease characterized by diminished levels or dysfunctional activity of C1-INH, leading to dysregulated
plasma kallikrein activity within the
kallikrein-
kinin pathway. Symptoms manifest as painful, potentially life-threatening swelling of subcutaneous tissues throughout the body and/or submucosal
edema in the upper airway or gastrointestinal tract. Attacks recur with unpredictable frequency, intensity, and duration, placing a heavy burden on patients' daily lives. Despite improved availability of medications for on-demand treatment during attacks and prophylaxis of future attacks, unmet needs remain.
Lanadelumab, a fully human
monoclonal antibody, may help address some of the limitations of existing prophylactic options (e.g., the need for
intravenous administration or frequent dosing). Preclinical studies demonstrate that it is highly potent and specifically inhibits
plasma kallikrein, and findings from phase Ia and Ib studies suggest this agent is well tolerated and provides sustained inhibition of
plasma kallikrein, allowing for less frequent dosing. The phase III HELP Study (NCT02586805) evaluating the efficacy and safety of
lanadelumab in preventing HAE attacks has been completed, and its open-label extension (NCT02741596) is ongoing.
Lanadelumab is now approved in the USA and Canada for prophylaxis to prevent attacks of HAE in patients aged ≥ 12 years. This review provides an overview of the discovery and clinical development of
lanadelumab, from preclinical through phase Ib studies, characterizing its safety/tolerability, efficacy, and pharmacokinetic and pharmacodynamic profiles. It also highlights how this agent may positively impact clinical care of patients with C1-INH-HAE.