Emerging drugs for antibody-mediated rejection after kidney transplantation: a focus on phase II & III trials

ABSTRACT

Introduction

Antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Its therapy continues to be challenge, and no treatment has been approved for the market thus far.

Areas covered

In this article, we discuss the pathophysiology and phenotypic presentation of ABMR, the current level of evidence to support the use of available therapeutic strategies, and the emergence of tailored drugs now being evaluated in systematic clinical trials. We searched PubMed, Clinicaltrials.gov and Citeline’s Pharmaprojects for pertinent information on emerging anti-rejection strategies, laying a focus on phase II and III trials.

Expert opinion

Currently, we rely on the use of apheresis for alloantibody depletion and intravenous immunoglobulin (referred to as standard of care), preferentially in early active ABMR. Recent systematic trials have questioned the benefits of using the CD20 antibody rituximab or the proteasome inhibitor bortezomib. However, there are now several promising treatment approaches in the pipeline, which are being trialed in phase II and III studies. These include interleukin-6 antagonism, CD38-targeting antibodies, and selective inhibitors of complement. On the basis of the information that has emerged so far, it seems that innovative treatment strategies for clinical use in ABMR may be available within the next 5–10 years.

KEYWORDS:

• Antibody-mediated rejection
• apheresis
• bortezomib
• clazakizumab
• complement blockade
• felzartamab
• imlifidase
• plasmapheresis
• tocilizumab
• transplantation

Funding

This paper was not funded.

Abbreviations

ABMR, antibody-mediated rejection

ATG, antithymocyte globulin

C1-INH, C1 esterase inhibitor

CyA, cyclosporin A

CYP, cytochrome P450

DGF, delayed graft function

DSA, donor-specific antibody

eGFR, estimated glomerular filtration rate

EMA, European Medicines Agency

FcγRIIIA, Fc-gamma receptor IIIA

FDA, Food and Drug Administration

HLA, human leukocyte antigen

IL-6, interleukin-6

IL-6R, interleukin-6 receptor

IVIG, intravenous immunoglobulin

KDIGO, Kidney Disease: Improving Global Outcomes

NK cell, natural killer cell

SOC, standard of care

Notes

1. In the pdf version, there is some re-formatting of Table 1 necessary: There seems to be (e.g. in the row B cells/Rtuximab) a shift of the lines. In the column Status of development, the text for each study should be in a line (e.g. Phase II (prematurely terminated)), so that the associated trial acronyms, identifiers and citations are correctly affiliated.