Vera's Atacicept Cuts IgA Nephropathy Proteinuria 42% vs Placebo in Phase 3, Published in NEJM

On Thursday, November 6, 2025, results from a Phase 3 trial of an experimental kidney drug were presented in the opening plenary session of the American Society of Nephrology's Kidney Week 2025. The same data were published at the same moment in The New England Journal of Medicine. The drug is atacicept, the trial is called ORIGIN 3, and the sponsor is Vera Therapeutics of Brisbane, California, which is listed on Nasdaq as VERA. The account here comes from Vera's own announcement.

The trial enrolled 431 adults with IgA nephropathy, a kidney disease. It was global, multicenter, randomized, double-blind and placebo-controlled. Participants were assigned one to one to either atacicept or placebo. The atacicept dose was 150 mg, self-injected at home under the skin once a week.

The primary endpoint was proteinuria, measured by the 24-hour urine protein-to-creatinine ratio, or UPCR, at a 36-week interim analysis. People on atacicept had a 46% reduction in UPCR from their own baseline. Compared with placebo, the reduction was 42%, which Vera describes as statistically significant and clinically meaningful.

Vera also reports on safety. In the ORIGIN 3 full analysis set, adverse events were generally balanced between the two groups. Serious adverse events were less frequent with atacicept, at one participant (0.5%), than with placebo, at 11 participants (5%). The company says there were no safety signals pointing to immunosuppression, and no deaths in either group. Across the wider ORIGIN program, it calls the safety profile favorable and comparable to placebo.

Atacicept is a fusion protein that blocks two cytokines, BAFF and APRIL, which help B cells survive and make the autoantibodies tied to IgA nephropathy, lupus nephritis and other autoimmune kidney diseases. Richard Lafayette, a Stanford nephrologist who directs its Glomerular Disease Center and was a primary investigator on ORIGIN 2b and ORIGIN 3, said ORIGIN 3 is the first Phase 3 trial of a B-cell modulator in IgAN to show improvements in proteinuria, Gd-IgA1 and hematuria. He said the consistent benefit and favorable safety suggest dual BAFF and APRIL inhibition may modify the disease course, and that he looks forward to the full two-year results.

The earlier ORIGIN Phase 2b trial met its primary and key secondary endpoints through 36 weeks, with proteinuria reductions and stable eGFR versus placebo. Through 96 weeks, Vera reports further gains in Gd-IgA1, hematuria and proteinuria, with eGFR stabilization. The FDA has granted atacicept Breakthrough Therapy Designation in IgAN based on the Phase 2b data. Vera says the drug has been given to more than 1,500 patients in trials across disease areas.

Marshall Fordyce, Vera's founder and CEO, said the results support the planned Biologics License Application. The company expects to file under the FDA's Accelerated Approval Program in the fourth quarter of 2025, with a possible PDUFA date in 2026 and a US launch that year. Bonnie Schneider, cofounder of the IgA Nephropathy Foundation, which she started in 2004, said patients have long feared kidney failure with few treatment options, and that she has never had more hope.

The ORIGIN 3 trial continues, blinded and placebo-controlled, to track kidney function by eGFR over two years, with completion expected in 2027. Atacicept is also being tested in the PIONEER trial in other kidney diseases, and ORIGIN Extend gives participants continued access. Vera's release carries the usual caveat that later trials may not match earlier ones and approval is not assured.