New Agents in Development for Sepsis: Any Reason for Hope?
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LEADING ARTICLE
New Agents in Development for Sepsis: Any Reason for Hope? Philippe Vignon1,2,3,5 · Pierre‑François Laterre4 · Thomas Daix1,2,3 · Bruno François1,2,3
© Springer Nature Switzerland AG 2020
Abstract Sepsis is a syndrome which is defined as a dysregulated host response to infection leading to organ failure. Since it remains one of the leading causes of mortality worldwide, numerous drug candidates have already been tested, and continue to be developed, as potential adjunct therapies. Despite convincing mechanisms of action and robust pre-clinical data, almost all drug candidates in the field of sepsis have failed to demonstrate clinical efficacy in the past two decades. Accordingly, the development of new sepsis drugs has markedly decreased in the past few years. Nevertheless, thanks to a better understanding of sepsis pathophysiology and pathways, new promising drug candidates are currently being developed. Instead of a unique sepsis profile as initially suspected, various phenotypes have been characterised. This has resulted in the identification of multiple targets for new drugs together with relevant biomarkers, and a better understanding of the most appropriate time to intervention. Within the entire sepsis drugs portfolio, those targeting the immune response are probably the most promising. Monoclonal antibodies targeting either cytokines or infectious agents are undoubtedly part of the potential successful therapeutic classes to come. Key points Identification of accurate biomarkers to better select appropriate phenotypes is essential to evaluate new drug candidates for the adjunctive treatment of sepsis More than 10 promising drugs are currently in clinical development in the sepsis field Immune response is probably one of the most appropriate targets to work on Several drugs, including monoclonal antibodies, are likely to be marketed in a near future
* Philippe Vignon [email protected] 1
Medical‑Surgical Intensive Care Unit, Dupuytren Teaching Hospital, 87000 Limoges, France
2
Inserm CIC 1435, Dupuytren Teaching Hospital, 87000 Limoges, France
3
Inserm UMR 1092, Dupuytren Teaching Hospital, 87000 Limoges, France
4
St Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate 12, 1200 Brussels, Belgium
5
Réanimation Polyvalente, CHU Dupuytren, 2 Avenue Martin Luther king, 87042 Limoges, France
1 Introduction Sepsis is one of the leading causes of mortality worldwide [1]. This syndrome is defined as a dysregulated host response to infection leading to organ dysfunction and failure [2]. With the exception of a short-lived therapy, namely the administration of recombinant activated protein C for severe sepsis [3], the majority of studied drugs have failed to improve sepsis-related mortality despite numerous encouraging preclinical data. It was probably a conceptual error to consider that a single therapeutic strategy or medication would provide an equal benefit to such a heterogeneous population with multiple underlying comorbidities, varia
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