Preclinical characterization and clinical development of ILARIS® (canakinumab) for the treatment of autoinflammatory diseases. (June 2016)

• Record Type: Journal Article
• Authors: Gram, Hermann
• Is Part Of: Current opinion in chemical biology. Volume 32(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-06
• Subjects: Bioorganic chemistry -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Clinical biochemistry -- Periodicals; Biochemistry -- Periodicals; Chimie bio-organique -- Périodiques; Biologie -- Périodiques; 572.05
• DOI: 10.1016/j.cbpa.2015.12.003
• Languages: English
• ISSNs: 1367-5931

Abstract

Highlights: Rare autoinflammatory syndromes display dyregulation of the inflammasome and IL-1β production. Canakinumab targets IL-1β and provides excellent clinical efficacy in autoinflammatory diseases. The X-ray structure of the canakinumab:IL-1β complex explains the molecular mode of action. PK/PD modeling predicts the dose regimen for canakinumab in CAPS. Abstract : Interleukin-1beta (IL-1β) is a pro-inflammatory cytokine which is part of the first line innate response in vertebrates and is induced in injury, infection, and immunity. While temporally limited induction of IL-1β is believed to protect the organisms against traumatic or infectious insults, its aberrant expression in chronic inflammation is detrimental. Therefore, pharmacological neutralization of IL-1β in chronic inflammatory diseases is a meaningful strategy to treat inflammation and to alleviate respective clinical symptoms in man. Canakinumab is a high-affinity human monoclonal antibody designed to target human IL-1β in inflammatory diseases. Indeed, canakinumab has shown excellent efficacy in rare genetic autoinflammatory diseases or pathological conditions associated with aberrant production of IL-1β. This review focuses on the molecular and clinical mode of action and pharmaceutical development of canakinumab in (auto)inflammatory diseases.