Therapeutic monoclonal antibodies with a focus on hereditary angioedema

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  • Zuraw Bruce L.
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego
  • Maurer Marcus
    Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology
  • Sexton Daniel J.
    Takeda Pharmaceutical Company Limited
  • Cicardi Marco
    Department of Biomedical and Clinical Sciences, Luigi Sacco, University of Milan, IRCCS ICS Maugeri

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Abstract

<p>Monoclonal antibodies (mAbs) have been shown to be effective and generally safe across a continually expanding list of therapeutic areas. We describe the advantages and limitations of mAbs as a therapeutic option compared with small molecules. Specifically, we discuss a novel mAb in the treatment of hereditary angioedema (HAE), a rare and potentially life-threatening condition characterized by recurrent unpredictable swelling attacks. HAE is mediated by dysregulation of plasma kallikrein activity leading to overproduction of bradykinin. Current prophylactic treatment for HAE includes androgens or replacement of the endogenous plasma kallikrein inhibitor, C1 inhibitor. However, there remains an unmet need for an effective, less burdensome treatment option. Lanadelumab is a fully human mAb targeting plasma kallikrein. Results from clinical trials, including a pivotal Phase 3 study and its ensuing open-label extension study, demonstrated that lanadelumab is associated with few treatment-related adverse events and reduced the rate of HAE attacks. This novel treatment option has the potential to significantly improve the lives of patients with HAE.</p>

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