Novel Drug Reduced Proteinuria by 46% in IgA Nephropathy Trial

At the American Society of Nephrology Kidney Week meeting, interim results from the phase III ORIGIN 3 trial showed that investigational atacicept (Vera) led to a 46% reduction in proteinuria at 36 weeks in patients with immunoglobulin A (IgA) nephropathy.

In this MedPage Today video, Sagar Nigwekar, MD, of Massachusetts General Hospital in Boston, explains the mechanism of action, study design, and the agent's potential role in this setting.

 So another exciting development at the recent Kidney Week meeting was the publication of interim data from a phase III trial of atacicept in patients with IgA nephropathy. And this trial was also published in the New England Journal of Medicine.

So atacicept is a native human transmembrane activator and calcium-modulator and cyclophilin-ligand interactor, all abbreviated as TACI. And it's a TACI-Fc fusion protein that inhibits two cytokines, the APRIL [a proliferation-inducing ligand] cytokine as well as the BAFF [B-cell activating factor] cytokine.

And so in this study that was published, which is a phase III study of atacicept, the investigators planned a double-blind, multicenter, randomized, placebo-controlled trial, and they enrolled patients with a biopsy-confirmed IgA nephropathy, and assigned them in a 1:1 ratio to receive either atacicept at a dose of 150 mg once a week, administered subcutaneously by patients at home, or matching placebo. And very similar to the trial of sibeprenlimab, they also looked at the percentage change from baseline in the urinary protein-to-creatinine ratio (UPCR), but this was analyzed at week 36 in the atacicept trial. And they also evaluated the safety.

So in this experiment, the investigators included 203 patients in this interim analysis. And what they note is, at week 36, the percent reduction from baseline in the UPCR was around 46% in the atacicept group and around 7% in the placebo group. So again, pretty substantial difference between the two groups and clearly favoring the atacicept.

This agent was also well tolerated and overall the frequency of adverse events was pretty comparable between the atacicept group and the placebo group.

So I think this is another exciting development, and again, similar to the previous agent I mentioned, confirms the key role that these cytokines play in the pathogenesis of IgA nephropathy, and also how the very targeted, innovative treatments can modulate these cytokines by inhibiting them. And then of course, conferring the advantages to the patients with IgA nephropathy.

https://www.medpagetoday.com/meetingcoverage/kidneyweekvideopearls/118855