Richard Lafayette, MD, Professor of Medicine at Stanford University, discusses the ORIGIN clinical trial evaluating atacicept in adults with IgA nephropathy (IgAN).
IgAN is a kidney disorder that occurs when IgA (immunoglobulin A) protein settles in the kidneys. In the early stages, IgA nephropathy has no symptoms. The first sign of this condition may be blood in the urine. End-stage kidney disease may develop. In most instances, the cause of this condition is unknown; however, certain disorders have been linked with IgA nephropathy, such as cirrhosis of the liver, celiac disease, and HIV infection.
Atacicept is an investigational recombinant fusion protein that contains the soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor that binds to the cytokines B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL). The treatment is designed to promote B-cell survival and autoantibody production associated with IgAN, lupus nephritis, and other autoimmune kidney diseases.
ORIGIN 3 Clinical Trial
The ORIGIN 3 clinical trial (NCT0471623) is a mult-part study comprising the origin phase 2b study as well as a separate pivotal phase 3 study evaluating the safety and efficacy of atacicept in adults with IgAN (N=431). Data was recently presented at the American Society of Nephrology (ASN) Kidney Week 2025 and published in the New England Journal of Medicine.
Atacicept met the primary endpoint of reduction in proteinuria at week 36 with atacicept-treated patients achieving a 46% reduction from baseline and 42% reduction compared to placebo. Proteinuria efficacy was consistent across prespecified subgroups of age, sex, race, region, baseline proteinuria, baseline estimated glomerular filtration rate, and baseline SGLT2i use. Improvements were also observed in secondary endpoints such as a 68% reduction in Gd-IgA1 and a resolvement of hematuria in 81% of participants with baseline hematuria.
The safety profile of atacicept appears favorable across the ORIGIN clinical program compared to placebo. In the ORIGIN 3 full analysis, fewer serious adverse events were reported with atacicept than placebo, and there were no safety signals indicating immunosuppression.
A submission of a Biologics License Application (BLA) through the Accelerated Approval Program to the U.S. Food and Drug Administration (FDA) is expected in quarter 4 of 2025. Additionally, the ORIGIN 3 trial will continue, with two-year results expected in 2027.
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To learn more about IgAN and other rare kidney conditions, visit https://checkrare.com/diseases/kidney-and-urinary-diseases/