Gram, Hermann (2019) The long and winding road in pharmaceutical development of canakinumab, a human anti-IL-1 antibody. Pharmacological Research.

Abstract

Abstract
Interleukin-1beta (IL-1) is an ancient and evolutionary conserved cytokine, which orchestrates in vertebrates innate immune responses triggered by infections. While temporally limited induction of IL-1 protects the organism against traumatic or infectious insults, its chronic production in unabated inflammation causes or enhances clinical manifestations of disease in almost all organ systems. Therefore, pharmacological targeting of IL-1 in a variety of clinical inflammatory conditions may provide symptomatic relief or profound disease modification. The discovery of proteolytic processing of the inactive pro-IL-1to mature, active and secreted IL-1 by the inflammasome/caspase I complex inspired drug discovery programs towards low molecular weight inhibitors across the Pharma industry. Approved and marketed IL-1 pathway drugs today, however, are biologics targeting either IL-1, or the IL-1 receptor. Canakinumab is a human monoclonal antibody that binds to human IL-1 with high affinity and neutralizes its biological activity. This review describes the unique preclinical and clinical development journey of canakinumab starting from a rare genetic autoinflammatory disease and a systemic juvenile form of arthritis to further rare monogenetic periodic fever syndromes, and leading to non-orphan diseases, such as gout, myocardial infarction, and lung cancer.

Item Type:	Article
Keywords:	canakinumab
Date Deposited:	05 Mar 2019 00:45
Last Modified:	05 Mar 2019 00:45
URI:	https://oak.novartis.com/id/eprint/38101