Atacicept Cuts IgAN Progression Risk 76% in ORIGIN 3 Final Data

Atacicept (Trutakna) stabilized kidney function and reduced kidney disease progression through 2 years in the final analysis of the phase 3 ORIGIN 3 trial in IgA nephropathy (IgAN), Vera Therapeutics announced.¹

Patients treated with atacicept had a mean estimated glomerular filtration rate (eGFR) change from baseline of -0.1 mL/min/1.73m2 at 52 weeks, compared with -5.7 mL/min/1.73m2 with placebo, a treatment effect of 5.6 mL/min/1.73m2 (95% CI, 3.7-7.5; P < .0001). Through 104 weeks, the annualized eGFR slope was -0.6 mL/min/1.73m2/year with atacicept versus -5.6 mL/min/1.73m2/year with placebo (P < .0001).

A composite kidney disease progression endpoint occurred in 11 patients on atacicept versus 38 on placebo, a 76% relative risk reduction (hazard ratio, 0.24; 95% CI, 0.12-0.48; P < .0001).

“The ORIGIN 3 final analysis, demonstrating a significant reduction in risk of composite kidney disease progression, true stabilization of eGFR, and a favorable safety profile through two years, marks a milestone in IgAN treatment,” Richard Lafayette, MD, professor of medicine, nephrology, and director of the Glomerular Disease Center at Stanford University Medical Center, and a principal investigator for ORIGIN 3, said in a statement.

IgAN Disease Burden

IgAN is an immune-mediated glomerular disease and a leading global cause of chronic kidney disease, most often diagnosed in adults between ages 30 and 40 years.¹ At least half of patients progress to kidney failure or death within 10 to 20 years of diagnosis, underscoring the interest in therapies that alter the disease's underlying course rather than only manage its symptoms.⁴

ORIGIN 3 Trial Design and Patient Population

ORIGIN 3 is a global, multicenter, randomized, double-blind, placebo-controlled phase 3 trial evaluating atacicept in adults with primary IgAN at risk for disease progression. The final efficacy analysis included 428 patients randomized 1:1 to atacicept 150 mg or placebo, self-administered once weekly at home by subcutaneous injection.

The trial's earlier 36-week interim analysis used proteinuria reduction as its primary endpoint and supported atacicept's accelerated approval in July 2026. The final analysis reported here followed patients through 104 weeks and added eGFR and composite kidney disease progression as efficacy endpoints, the longer-term data the FDA had indicated it would need before considering full approval.

Full Results From the Final ORIGIN 3 Analysis

No patients in the atacicept arm reached the trial's more severe endpoint of dialysis for 30 days or longer, transplantation, or death, compared with 8 patients on placebo. Investigators noted the eGFR findings align with the Kidney Disease: Improving Global Outcomes (KDIGO) 2025 guideline goal of slowing kidney function decline toward the physiologic rate of less than 1 mL/min/1.73m2 per year.²

Atacicept also produced statistically significant reductions across hierarchically tested secondary endpoints, including proteinuria, galactose-deficient IgA1, and hematuria.

Safety findings through 2 years were consistent with earlier results from the ORIGIN program.³ Overall adverse event and infection rates were similar between arms, with no cases of opportunistic infection or clinically relevant hypogammaglobulinemia. Detailed results are expected to be presented at an upcoming scientific congress, and the final analysis has not yet undergone independent peer review.

Atacicept Mechanism and What's Next for Full Approval

Atacicept is a soluble recombinant fusion protein built on the transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor. It binds and neutralizes BAFF and APRIL, cytokines implicated in the B-cell activation that drives IgAN pathophysiology. Because atacicept is immunosuppressive, concomitant use with other immune-modulating therapies, including systemic corticosteroids, has not been formally evaluated, and live vaccines are not recommended within 30 days of treatment initiation or during therapy.

Atacicept's current indication, reducing proteinuria in adults with primary IgAN at risk for disease progression, is under accelerated approval; it has not been established whether atacicept slows kidney function decline over the long term. Vera Therapeutics said the ORIGIN 3 final analysis will support a supplemental biologics license application it plans to submit to the FDA in the fourth quarter of 2026, seeking full approval with a possible decision in 2027.

References

1. Vera Therapeutics. Vera Therapeutics announces TRUTAKNA (atacicept-vymj) stabilized eGFR and prevented kidney disease progression through two years in ORIGIN 3 final efficacy analysis in IgA nephropathy. News release. September 15, 2026.

2. Lafayette R, Barbour SJ, Brenner RM, et al. A phase 3 trial of atacicept in patients with IgA nephropathy. N Engl J Med. 2026;394(7):647-657. doi:10.1056/NEJMoa2510198

3. Kidney Disease: Improving Global Outcomes (KDIGO) IgAN and IgAV Work Group. KDIGO 2025 clinical practice guideline for the management of immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV). Kidney Int. 2025;108(4S):S1-S71.

4. Pitcher D, Braddon F, Hendry B, et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2023;18(6):727-738. doi:10.2215/CJN.0000000000000135