Lanadelumab for the treatment of hereditary angioedema

ABSTRACT

Introduction: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare yet still probably underdiagnosed clinical condition. Recurrent episodes of subcutaneous and sub-mucosal swelling may involve the skin, the gastrointestinal tract or even the upper airways, exposing the patients to the risk of death. With the aim of improving patients’ quality of life, the therapeutic scenario has expanded over the years.

Areas covered: The focus of the present review is lanadelumab, a fully human, κ-light-chain, monoclonal immunoglobulin G1 against plasma kallikrein, currently approved for long-term prophylaxis of C1-INH-HAE attacks in the USA and Canada and designated as an orphan drug by the European Medicines Agency.

Expert opinion: Lanadelumab is able to inhibit plasma kallikrein with high selectivity and affinity. The subsequent phases of drug development and the ongoing open-label trial have proven its safety and efficacy. It overcomes some of the limitations of other drugs available for long-term prophylaxis, given the easy route of administration, the simple administration schedule and the possibility to tailor the treatment to each patient. Further studies are needed to test its efficacy also in other types of angioedema for which a central role of plasma kallikrein is envisaged.

KEYWORDS:

• C1 inhibitor deficiency
• efficacy
• hereditary angioedema
• kallikrein
• lanadelumab
• monoclonal immunoglobulin
• prophylaxis
• safety

Article highlights

• Despite several therapeutic options available, the burden of hereditary angiodema due to C1-INH deficiency is still not negligible, with remarkable impact on patients’ quality of life.

• Lanadelumab (brand name Takhzyro) is a fully human, κ-light-chain, monoclonal immunoglobulin G1 able to inhibit plasma kallikrein with high selectivity and affinity.

• The safety and efficacy of lanadelumab for long-term prophylaxis of acute C1-INH-HAE attacks has been demonstrated in many clinical trials.

• Lanadelumab has been recently approved for long-term prophylaxis in patients 12 years of age and older in the USA and Canada and it is designated as an orphan drug by the European Medicines Agency.

Box 1. Drug Summary Box

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Acknowledgments

I would like to heartily thank my Mentor, Prof Marco Cicardi, who always trusted me and guided me along the challenging clinical and research pathway over all these years, teaching me the importance of curiosity associated with intellectual and ethical integrity in science as well as in life. I dedicate this paper to his memory.

Declaration of interest

MA Wu has performed clinical research for and reports receiving meeting sponsorship from Shire/Takeda. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One of the reviewers on this manuscript has received research funding, but no consulting fees, from Shire/Takeda in the past for basic sciences studies unrelated to the preclinical or clinical development of lanadelumab. Another reviewer on this manuscript has received non-financial support from Shire Deutschland GmbH, CSL Behring and has received personal fees from Shire Deutschland GmbH, CSL Behring. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.