Atacicept in IgA Nephropathy - Phase 3 Trial Final Efficacy Analysis

Key numbers

• 95% confidence interval
• 95% CI
• 7.0% and 15.4%

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.).

Jonathan Barratt, Robert M Brenner, Sean J Barbour, Kirk N Campbell, Tom Doan, Necmi Eren, Jürgen Floege, Marshall W Fordyce, Vivekanand Jha, Zeeshan Khawaja, Beom Seok Kim, Adrian Liew, Bart Maes, Atanu Pal, Roberto Pecoits-Filho, Richard K S Phoon, Dana V Rizk, Hitoshi Suzuki, Vladimír Tesař, Hernán Trimarchi, Xuelian Wei, Lixi Yu, Hong Zhang, Richard Lafayette, ORIGIN Phase 3 Trial Investigators

Leverage2 / 5

Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).

10% of this desk’s rubric

Magnitude3 / 5

Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.

20% of this desk’s rubric

Evidence5 / 5

Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.

32% of this desk’s rubric

Novelty3 / 5

A genuinely new approach to an open problem.

8% of this desk’s rubric

Trajectory2 / 5

Some room to improve with obvious engineering.

5% of this desk’s rubric

Stakes2 / 5

Benefits a professional community (practitioners, clinicians, engineers).

25% of this desk’s rubric

• Citations0 (reference 20, via openalex, Oct 25, 2026, 06:17 UTC)

• Reviewed by heuristic-v10 on Oct 25, 2026, 06:17 UTC. Paper type: clinical.
• Categories: Journal Article
• BRIEF, No.3 in the Medicine edition of October 25, 2026.