Understanding Atacicept & 36-Week ORIGIN 3 Data from Kidney Week 2025, With Jonathan Barratt, MBChB, PhD

Interim data from the phase 3 ORIGIN 3 trial suggest atacicept reduced urinary protein-to-creatinine ratio by 45.7% from baseline to week 36 in patients with IgA nephropathy (IgAN), representing a 41.8-percentage-point difference compared with placebo.

Presented at the American Society of Nephrology (ASN) Kidney Week 2025 and simultaneously published in the New England Journal of Medicine, the 36-week data offer the nephrology community evidence of the efficacy of atacicept, a dual BAFF/APRIL inhibitor, in adults with IgAN.

“ORIGIN 3 is the first Phase 3 clinical trial of a B-cell modulator in IgAN to show clinical improvements in proteinuria, Gd-IgA1, and hematuria. The consistent benefit for key disease markers and favorable safety profile across the ORIGIN program suggests that dual BAFF and APRIL inhibition with atacicept may modify disease course by targeting the underlying pathophysiology. I look forward to the full two-year results of the trial,” said Richard Lafayette, MD, professor of Medicine and Nephrology as well as the director of the Glomerular Disease Center at Stanford University Medical Center and a primary investigator for both ORIGIN 2b and ORIGIN 3.

The presentation follows Vera Therapeutics’ June 2025 announcement of the trial’s primary endpoint results. In a November 2025 update, Marshall Fordyce, MD, founder and CEO of Vera Therapeutics, confirmed the company’s plans to submit a Biologics License Application to the FDA in Q4 2025, targeting a potential commercial launch in 2026.

The ORIGIN 3 trial is an ongoing, global, multicenter, randomized, double-blind, placebo-controlled study that enrolled 431 adults with IgAN. Participants were randomized 1:1 to receive atacicept 150 mg once weekly via subcutaneous injection or placebo, alongside standard-of-care therapy. The study is designed to monitor kidney function and disease progression over 2 years, with final results expected in 2027.

At 36 weeks, atacicept produced additional meaningful improvements in key biomarkers and clinical outcomes. Galactose-deficient IgA1 (Gd-IgA1) levels decreased by 68.3% from baseline, compared with 2.9% in the placebo group, with reductions evident as early as week 4. Dipstick hematuria resolution was achieved in 81.0% of atacicept-treated patients versus 20.7% with placebo. In addition, urinary albumin-to-creatinine ratio decreased by 47.3% with atacicept compared with 8.8% for placebo.

In the safety population (n=214 per arm), median treatment exposure was 34 weeks for atacicept and 31 weeks for placebo. Adverse events occurred in 59.3% and 50.0% of patients, respectively. Injection-site reactions were more frequent with atacicept (19.2% vs 1.9%), whereas serious adverse events were less common (0.5% vs 5.1%) and no deaths were reported.

For more on the results, check out this special edition episode of Kinsey Compass: Navigating Clinical Trials, with Lafayette from the conference floor at Kidney Week 2025.

Relevant disclosures of interest for Barratt included Argenx, Calliditas Therapeutics, Chinook Therapeutics, Galapagos NV, GSK, Novartis, Travere Therapeutics, and others.

References:

1. Lafayette R, Barbour SJ, Brenner RM, et al. ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.

2. Vera Therapeutics. Vera Therapeutics Announces Positive ORIGIN Phase 3 Data for Atacicept in IgA Nephropathy Presented at ASN Kidney Week 2025 and Published in the New England Journal of Medicine | Vera Therapeutics. Vera Therapeutics. Published November 6, 2025. Accessed November 6, 2025. https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-positive-origin-phase-3-data