Atacicept in IgA Nephropathy - Phase 3 Trial Final Efficacy Analysis

Why clinicians should know about it

• Picked for Nephrology (paper of the day, 24 October 2026): Phase 3 RCT, slows eGFR decline in IgA nephropathy

Abstract

BACKGROUND: Atacicept resulted in a significantly greater reduction in the urinary protein-to-creatinine ratio than placebo in a previously published analysis of this trial, ORIGIN 3. Final prespecified efficacy results are reported here. METHODS: We randomly assigned adults with biopsy-confirmed IgA nephropathy to receive weekly subcutaneous atacicept at a dose of 150 mg or placebo. We carried out final analyses of two secondary end points: the change in the estimated glomerular filtration rate (eGFR) at week 52 and the annualized eGFR slope through week 104; additional hierarchically tested end points and safety were assessed. RESULTS: Of 431 patients who underwent randomization, 428 received atacicept or placebo (214 per group). At week 52, the mean change in the eGFR was -0.11 ml per minute per 1.73 m2 of body-surface area (95% confidence interval [CI], -1.44 to 1.22) with atacicept and -5.69 ml per minute per 1.73 m2 (95% CI, -7.04 to -4.35) with placebo (mean difference, 5.58 ml per minute per 1.73 m2; 95% CI, 3.68 to 7.48; P<0.001). Through week 104, the mean annualized eGFR slope was -0.60 ml per minute per 1.73 m2 (95% CI, -1.62 to 0.41) with atacicept and -5.60 ml per minute per 1.73 m2 (95% CI, -6.64 to -4.57) with placebo (difference, 5.00 ml per minute per 1.73 m2 per year; 95% CI, 3.55 to 6.45; P<0.001). Composite kidney-disease progression occurred in 11 patients (5.1%) in the atacicept group and in 38 patients (17.8%) in the placebo group (hazard ratio, 0.24; 95% CI, 0.12 to 0.48; P<0.001); no patients in the atacicept group had progression to dialysis, transplantation, or death, as compared with 7 patients in the placebo group. Adverse events occurred in 160 of 214 patients (74.8%) in the atacicept group and in 167 of 214 patients (78.0%) in the placebo group; serious adverse events occurred in 7.0% and 15.4%, respectively. One patient (in the placebo group) died. CONCLUSIONS: Atacicept slowed and stabilized the decline in the eGFR as compared with placebo. (Funded by Vera Therapeutics; ORIGIN 3 ClinicalTrials.gov number, NCT04716231.).

Abstract as published, via PubMed.