New Agents in Development for Sepsis: Any Reason for Hope?

Drugs. 2020 Nov;80(17):1751-1761. doi: 10.1007/s40265-020-01402-z.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Bacteria / drug effects
  • Bacteria / pathogenicity
  • Biomarkers / analysis
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Combined Modality Therapy / methods
  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Host Microbial Interactions / drug effects
  • Host Microbial Interactions / immunology
  • Humans
  • Molecular Targeted Therapy / methods
  • Pathogen-Associated Molecular Pattern Molecules / antagonists & inhibitors
  • Sepsis / diagnosis
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Sepsis / microbiology
  • Stem Cell Transplantation*
  • Treatment Outcome
  • Virulence Factors / antagonists & inhibitors

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Biomarkers
  • Cytokines
  • Pathogen-Associated Molecular Pattern Molecules
  • Virulence Factors