Jonathan Barratt, PhD, FRCP, Professor of Renal Medicine, University of Leicester, UK, describes the latest results of a phase 2b trial examining atacicept to treat immunoglobulin A (IgA) nephropathy.
IgA nephropathy is a rare kidney disease characterized by build-up of IgA deposits. This buildup causes inflammation and damage to the glomeruli, which in turn causes hematuria and proteinuria. This damage may lead to scarring of the nephrons which progresses slowly over many years. Eventually, IgA nephropathy can lead to end-stage kidney disease.
As Dr. Barratt explains, atacicept is an investigational recombinant fusion protein that binds to the cytokines B lymphocyte stimulator (BlyS) and a proliferation-inducing ligand (APRIL). These cytokines promote B-cell survival and autoantibody production associated with certain autoimmune diseases, including IgA nephropathy. The ORIGIN trial is a multinational, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of atacicept in patients with IgAN who continue to have persistent proteinuria and remain at high risk of disease progression despite being on a stable prescribed regimen of RAASi for at least 12 weeks at the highest available/tolerated dose. The objectives of the study are to determine the effect of atacicept on proteinuria and preservation of renal function compared to placebo to determine the appropriate dose for further clinical development. The primary endpoint is the change in proteinuria as evaluated by UPCR at week 24 and the key secondary endpoint is the change in proteinuria as evaluated by UPCR at week 36.
Vera Therapeutics recently announced results from a PP analysis of the ORIGIN trial. In this analysis, the population was defined as patients who had completed treatment according to protocol (n=102), where 14 patients who had protocol violations identified by a blinded third-party CRO were excluded.
In the prespecified per protocol analysis, patients given atacicept 150 mg for 24 weeks achieved a 41% mean reduction in proteinuria versus baseline and a 34% delta versus placebo (p=0.025). With interim data at Week 36, the atacicept 150 mg dose group achieved a 47% mean reduction in proteinuria from baseline and a 48% delta versus placebo.
Safety results indicated that atacicept was generally well-tolerated and were consistent with the previously observed safety profile of atacicept, including a 1% discontinuation rate due to adverse events (AEs) and comparable rates of infection compared to placebo. Serious treatment-emergent AEs were observed in 2% of patients in all atacicept arms and in 9% of patients in the placebo arm.
To learn more about IgA nephropathy and other rare kidney diseases, visit checkrare.com/diseases/kidney
