Atacicept in IgA Nephropathy — Phase 3 Trial Final Efficacy Analysis

Abstract

BackgroundAtacicept 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. MethodsWe 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. ResultsOf 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. ConclusionsAtacicept slowed and stabilized the decline in the eGFR as compared with placebo. (Funded by Vera Therapeutics; ORIGIN 3 ClinicalTrials.gov number, NCT04716231.)