Half-life extended biotherapeutics

INTRODUCTION: Many of the biotherapeutics approved or under development suffer from a short half-life necessitating frequent applications in order to maintain a therapeutic concentration over an extended period of time. The implementation of half-life extension strategies allows the generation of long-lasting therapeutics with improved pharmacokinetic and pharmacodynamic properties. AREAS COVERED: This review gives an overview of the different half-life extension strategies developed over the past years and their application to generate next-generation biotherapeutics. It focuses on srategies already used in approved drugs and drugs that are in clinical development. These strategies include those aimed at increasing the hydrodynamic radius of the biotherapeutic and strategies which further implement recycling by the neonatal Fc receptor (FcRn). EXPERT OPINION: Half-life extension strategies have become an integral part of development for many biotherapeutics. A diverse set of these strategies is available for the fine-tuning of half-life and adaption to the intended treatment modality and disease. Currently, half-life extension is dominated by strategies utilizing albumin binding or fusion, fusion to an immunoglobulin Fc region and PEGylation. However, a variety of alternative strategies, such as fusion of flexible polypeptide chains as PEG mimetic substitute, have reached advanced stages and offer further alternatives for half-life extension.