Lanadelumab for the prevention of attacks in hereditary angioedema

ABSTRACT

Introduction: Hereditary angioedema (HAE) with C1 esterase inhibitor deficiency (C1-INH-HAE) is a rare disease that manifests with cutaneous and/or submucosal swellings due to uncontrolled activation of the contact/kinin system. Attacks recur with unpredictable frequency and severity, laryngeal edema is potentially lethal, and the disease burden may severely disrupt patients’ lives.

Areas covered: This review provides an overview of lanadelumab, a human monoclonal antibody targeted against plasma kallikrein that was recently approved for prevention of symptoms in C1-INH-HAE.

Expert opinion: The phase III HELP Study demonstrated the efficacy of lanadelumab in reducing HAE attacks. These positive results are being further confirmed in the open-label extension study. This agent addresses some of the limitations of existing prophylactic options as tolerability issues, the need for intravenous administration and frequent dosing. Therefore, lanadelumab can profoundly improve the quality of life of patients with C1-INH-HAE.

KEYWORDS:

• Hereditary angioedema
• chronic disease
• lanadelumab
• clinical efficacy
• safety
• tolerability
• cost-effectiveness
• C1 inhibitor deficiency

Article highlights

• Lanadelumab (initially called DX-2930) is a fully human, κ-light-chain, monoclonal immunoglobulin G1, designed to selectively bind plasma kallikrein with a very high affinity

• It is the first human monoclonal antibody licensed to prevent angioedema attacks in C1-INH-HAE patients

• Safety and efficacy of lanadelumab was demonstrated in several controlled clinical trials, and an open-extension study

• This agent addresses some of the limitations of existing prophylactic options and can profoundly improve disease control and quality of life of patients with C1-INH-HAE

• Future evidence will be gathered to quantify individual and societal benefit, long-term safety, and cost-effectiveness over time.

Information resourses

https://www.ema.europa.eu/en/medicines/human/EPAR/takhzyro#authorisation-details-section

https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-new-treatment-rare-hereditary-disease

https://www.int.takhzyro.com//

https://clinicaltrials.gov/ct2/results?cond=&term=lanadelumab&cntry=&state=&city=&dist=

Declaration of interest

A Valerieva reports being a participant in a grant from the Bulgarian Ministry of Science under the National Program for Research ‘Young Scientists and Postdoctoral Students’, personal fees from Shire/Takeda, Pharming Group N.V., CSL Behring, Astra Zeneca, Berlin-Chemie/Menarini Group, Teva, Novartis. M Cicardi reports receiving grants from Shire and personal fees from Alnylam, BioCryst Pharmaceuticals, Inc., CSL Behring, KalVista, Pharming Technologies BV, Shire, and Adverum. M A Wu reports personal fees from Shire/Takeda, CSL Behring, and BioCryst, outside the submitted work. Senter R reports personal fees from Shire/Takeda, CSL Behring, BioCryst, Novartis, outside the submitted work. A Zanichelli reports personal fees from CSL Behring, Pharming Group NV, and Shire/Takeda, and performing clinical research for BioCryst, CSL Behring, Pharming Group NV, and Shire/Takeda. The authors have 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

Takeda provided a scientific accuracy review at the request of the journal editor. One reviewer declares having received research funding, but no consulting fees, from Shire/Takeda in the recent past for basic sciences studies unrelated to the clinical development of lanadelumab. One reviewer declares having been a consultant for Shire (now Takeda) in the past. One reviewer declares non-financial support and personal fees from Shire Deutschland GmbH and CSL Behring. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.