ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN

Background: IgA nephropathy (IgAN) is a B-cell mediated immune complex glomerulonephritis. Atacicept is a native human TACI-Fc fusion protein that binds and inhibits B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), key immunoregulatory cytokines central to the pathophysiology of IgAN, thereby modulating B-cell activity. Methods: In this ongoing double-blind, placebo-controlled, multinational Phase 3 trial, patients with biopsy-proven IgAN were randomized 1:1 to 150 mg of atacicept, self-administered subcutaneously once weekly at home, or placebo. The primary endpoint was percentage change from baseline (BL) at Week 36 in the urinary protein-to-creatinine ratio (UPCR) from a 24-hour collection. Secondary endpoints of galactose-deficient IgA1 (Gd-IgA1) percentage change from BL, hematuria resolution, and safety were also evaluated. Results: The interim analysis included 203 patients (atacicept n=106; placebo n=97). At Week 36, atacicept treatment resulted in a 45.7% UPCR reduction from BL vs. a 6.8% reduction with placebo, with a statistically significant 41.8% (95% CI, 28.9%–52.3%; P<0.0001) treatment difference (Figure). Significant improvements were also observed in Gd-IgA1 and hematuria with atacicept (Figure). The incidence of adverse events was similar between both groups, and most were mild or moderate. Conclusion: Atacicept treatment resulted in a statistically significant proteinuria reduction compared with placebo at Week 36, as well as Gd-IgA1 reduction, hematuria improvement, and a favorable safety profile. The results demonstrate the potential for atacicept to address the underlying pathophysiology of IgAN and provide a targeted, disease-modifying therapy. Funding: Commercial Support - Vera Therapeutics, Inc.