IgA nephropathy: an overview of drug treatments in clinical trials

ABSTRACT

Introduction

IgA nephropathy (IgAN) is the commonest primary glomerulonephritis worldwide and may progress to end-stage kidney disease (ESKD) within a 10–20 year period. Its slowly progressive course has made clinical trials challenging to perform, however the acceptance of proteinuria reduction as a surrogate end point has significantly improved the feasibility of conducting clinical trials in IgAN, with several novel and repurposed therapies currently undergoing assessment. Already, interim results are demonstrating value to some of these, offering great hope to those with IgAN.

Areas covered

This review explores the rationale, candidates, clinical precedents, and trial status of therapies that are currently or have recently been evaluated for efficacy in IgAN. All IgAN trials registered with the U.S. National Library of Medicine; ClinicalTrials.gov were reviewed.

Expert opinion

For the first time, effective treatment options beyond supportive care are becoming available for those with IgAN. This is the culmination of commendable international efforts and signifies a new era for those with IgAN. As more therapies become available, future challenges will revolve around deciding which treatments are most appropriate for individual patients, which is likely to push IgAN into the realm of precision medicine.

KEYWORDS:

• IgA nephropathy
• clinical trials
• BAFF
• APRIL
• complement
• gut
• monoclonal antibodies
• RNA interference

Article highlights

• IgA nephropathy is a primary glomerular disease which progresses to end-stage kidney disease (ESKD) in 20-40% of those affected.

• The typical slow progression of this disease has impeded the introduction of new treatments, owing to the logistical challenges associated with prolonged clinical trials

• The demonstration and acceptance of proteinuria reduction as a surrogate marker for ESKD has significantly improved the feasibility of conducting clinical trials in IgAN

• Several novel and repurposed therapies are currently being evaluated, with TRF-Budesonide becoming the first to receive accelerated approval by the United States Food and Drug Administration

This box summarizes key points contained in the article.

Declaration of interest

G Gonzalez-Martin declares no conflict of interest to declare while H Selvaskandan is a Kidney Research UK Clinical Research fellow who has received research funding from Omeros. CK Cheung reports having consultancy agreements with Calliditas and George Clinical; reports receiving honoraria from Vifor Pharma; and reports receiving research funding from GlaxoSmithKline and Travere Therapeutics. J Barratt reports having consultancy agreements with Astellas, Alnylam, BioCryst, Calliditas, Chinook, Dimerix, Novartis, Omeros, Travere Therapeutics, Vera Therapeutics and Visterra; reports receiving research funding from Argenx, Calliditas, Chinook, Galapagos, GlaxoSmithKline, Novartis, Omeros, Travere Therapeutics and Visterra; and reports being a scientific advisor or member via the Editorial Board of CJASN, Glomerular Diseases & Clinical Science and Kidney International. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.