Atacicept Cuts Proteinuria 46% in Phase 3 ORIGIN Trial for IgA Nephropathy, Setting Up a July FDA Decision

Overview

Atacicept, an experimental antibody that blocks two B-cell survival signals at once, significantly reduced proteinuria compared with placebo at week 36 in adults with IgA nephropathy, according to the Phase 3 ORIGIN 3 trial published in the New England Journal of Medicine. The interim analysis, summarized by Cleveland Clinic Journal of Medicine, reported a 45.7% reduction in the 24-hour urinary protein-to-creatinine ratio with atacicept versus 6.8% with placebo. The result positions developer Vera Therapeutics for a U.S. Food and Drug Administration accelerated-approval decision with a target action date of July 7, 2026, as reported by Pharmacally.

What We Know

IgA nephropathy is one of the leading causes of glomerulonephritis and renal failure, according to StatPearls, which notes that approximately 10% of renal biopsies in the United States reveal the disease, with prevalence higher in East Asia (up to 40% of biopsies) and Europe (20% to 30% of biopsies). Between 20% and 50% of affected patients develop end-stage renal disease within 20 years of diagnosis, the same reference states. Immune complexes composed of galactose-deficient IgA1 are central in the circulation and glomeruli of individuals with the disease.

Atacicept targets that upstream biology. The drug binds the cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), as described by StockTitan in its report on Vera’s FDA-alignment announcement.

The ORIGIN 3 interim analysis included 203 patients with IgA nephropathy randomized to atacicept 150 mg self-administered subcutaneously once weekly, or placebo, according to Cleveland Clinic Journal of Medicine. The breakdown was 106 patients receiving atacicept and 97 receiving placebo, as reported by NephJC.

On the primary endpoint, the percentage reduction in the urinary protein-to-creatinine ratio at week 36 was 45.7% with atacicept and 6.8% with placebo, a between-group difference of 41.8 percentage points (P < .001), according to Cleveland Clinic Journal of Medicine. That geometric mean difference of 41.8 percentage points carried a 95% confidence interval of 28.9 to 52.3, as documented in the trial record published by the Icahn School of Medicine at Mount Sinai.

Secondary measures moved in the same direction. Galactose-deficient IgA1 levels decreased by 68.3% with atacicept and 2.9% with placebo, with reductions evident as early as week 4, according to Cleveland Clinic Journal of Medicine. Hematuria resolved in 81.0% of the atacicept group and 20.7% of the placebo group, the same source reported.

The safety profile was comparable between arms. Adverse events were mostly mild, occurring in 59.3% of atacicept-treated patients and in 50.0% of placebo-treated patients, according to Cleveland Clinic Journal of Medicine. NephJC noted that serious treatment-emergent adverse events were less frequent with atacicept than with placebo, as summarized in its review of the ORIGIN 3 data.

The trial was published in the New England Journal of Medicine; the print version appeared February 12, 2026, in Volume 394, Issue 7, pages 647-657, under DOI 10.1056/NEJMoa2510198, per the citation recorded by the Icahn School of Medicine at Mount Sinai. The data were presented at the American Society of Nephrology Kidney Week 2025 in Houston, according to Cleveland Clinic Journal of Medicine.

Regulatory Path

The FDA accepted Vera Therapeutics’ Biologics License Application for atacicept and granted Priority Review for the treatment of adults with IgA nephropathy, setting a Prescription Drug User Fee Act target action date of July 7, 2026, according to Pharmacally. The application was submitted under the Accelerated Approval pathway, the same outlet reported.

If approved, atacicept could become the first B-cell modulator in IgA nephropathy to target both BAFF and APRIL, Pharmacally reported. “We are excited for the potential to deliver the first approved therapy targeting both BAFF and APRIL in adults with IgAN,” said Marshall Fordyce, M.D., founder and CEO of Vera Therapeutics, in comments reported by StockTitan.

That distinction matters because a related therapy already reached the market. In November 2025, sibeprenlimab received FDA accelerated approval to reduce proteinuria in adults with primary IgA nephropathy at risk for disease progression, according to Pharmacy Times. Sibeprenlimab, marketed as Voyxact by Otsuka, is a first-in-class monoclonal antibody that inhibits APRIL, the same review noted. Atacicept’s mechanism adds BAFF blockade to that target.

What We Don’t Know

The headline ORIGIN 3 result rests on proteinuria, a surrogate marker, rather than on a direct measure of kidney function. NephJC flagged that the major limitation of the interim report is the lack of estimated glomerular filtration rate (eGFR) data, in its review of the ORIGIN 3 trial. That gap is the reason atacicept is being reviewed under the accelerated pathway rather than for full approval.

Vera has said it aligned with the FDA on a revised, earlier ORIGIN 3 eGFR analysis plan, with eGFR results now expected in the third quarter of 2026 and a supplemental BLA for full approval planned for the fourth quarter of 2026, according to StockTitan. Whether the eGFR data confirm a durable slowing of kidney-function decline — the outcome that ultimately matters for patients facing end-stage renal disease — remains to be seen.