Recent early clinical drug development for acute kidney injury

ABSTRACT

Introduction: Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI.

Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719.

Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.

KEYWORDS:

• Acute kidney injury
• alkaline phosphatase
• α-melanocortin receptor 1
• bone morphogenetic protein receptor
• cardiac surgery AKI
• delayed graft function
• hepatocyte growth factor
• p53
• sepsis associated AKI

Article highlights

• Comprehensive review of agents currently in clinical trial for transplant, sterile and sepsis associated AKI

• Up to date information on trial progress

• Review of AC607 and ABT-719 two recent failed drugs

• Integration of new pathophysiological understanding of cell death pathways with current agents

• Expert opinion on the way forward in therapeutics for AKI

This box summarizes key points contained in the article.

Declaration of interest

K. Gallagher has been supported by a clinical research training fellowship jointly funded by the Medical Research Council UK, Kidney Research UK and GlaxoSmithKline. J. Hughes has acted as a member of advisory boards for GlaxoSmithKline and UCB. E. Harrison has acted as a member of a GlaxoSmithKline advisory board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.