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A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy.

A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy. The New England journal of medicine Lafayette, R., Barbour, S. J., Brenner, R. M., Campbell, K. N., Doan, T., Eren, N., Floege, J., Jha, V., Kim, B. S., Liew, A., Maes, B., Pal, A., Pecoits-Filho, R., Phoon, R. K., Rizk, D. V., Suzuki, H., Tesar, V., Trimarchi, H., Wei, X., Zhang, H., Barratt, J., ORIGIN Phase 3 Trial Investigators 2025

Abstract

BACKGROUND: IgA nephropathy, the most common primary glomerulopathy worldwide, is a kidney disorder of B-cell origin characterized by mesangial accumulation of IgA-containing immune complexes. In at least 50% of patients, IgA nephropathy leads to kidney failure or death within 10 to 20 years after diagnosis. Atacicept is a native human transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI)-Fc fusion protein that inhibits two key immunoregulatory cytokines - B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) - that are thought to be central to the pathophysiology of IgA nephropathy.METHODS: In this ongoing, phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients with IgA nephropathy in a 1:1 ratio to receive atacicept at a dose of 150 mg once weekly, administered subcutaneously by patients at home, or matching placebo. The primary end point was the percentage change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 36. Safety was also evaluated.RESULTS: A total of 203 patients were included in the prespecified interim analysis: 106 patients in the atacicept group and 97 in the placebo group. At week 36, the percentage reduction from baseline in the urinary protein-to-creatinine ratio was 45.7% in the atacicept group and 6.8% in the placebo group, with a geometric mean between-group difference of 41.8 percentage points (95% confidence interval, 28.9 to 52.3; P<0.001). Adverse events were observed in 59.3% of the patients in the atacicept group and in 50.0% in the placebo group; most were mild or moderate in severity.CONCLUSIONS: In this prespecified interim analysis, treatment with atacicept resulted in a significantly greater reduction in proteinuria than placebo at week 36 in patients with IgA nephropathy. (Funded by Vera Therapeutics; ORIGIN 3 ClinicalTrials.gov number, NCT04716231.).

View details for DOI 10.1056/NEJMoa2510198

View details for PubMedID 41196369