Atacicept Significantly Reduces Proteinuria in IgA Nephropathy: Phase 3 Trial Results

Researchers have found in phase 3 ORIGIN 3 trial that investigational dual BAFF/APRIL inhibitor atacicept significantly reduced proteinuria in patients with immunoglobulin A nephropathy (IgAN). The randomized, double-blind, placebo-controlled study involved 431 patients receiving either atacicept 150 mg or placebo weekly via subcutaneous injection.

The primary outcome measured was the change in 24-hour urine protein-to-creatinine ratio (UPCR) at 36 weeks, demonstrating notable improvement with atacicept treatment.

Participants treated with atacicept achieved a 46% reduction from baseline in proteinuria as measured by 24-hour urine protein-to-creatinine ratio (UPCR), with a statistically significant and clinically meaningful 42% reduction in UPCR compared to placebo (p<0.0001) at week 36. For other prespecified endpoints, atacicept treatment also demonstrated results that were consistent with or better than those previously observed in the ORIGIN Phase 2b trial. The safety profile of atacicept in this analysis was favorable, and comparable to placebo. Vera plans to share these results with the FDA in the coming weeks, and full results will be submitted to the American Society of Nephrology Kidney Week.

“ORIGIN 3 is the first Phase 3 clinical trial in IgAN to demonstrate this magnitude of UPCR reduction compared to placebo at week 36. These results convincingly demonstrate the impact of atacicept to reduce proteinuria,” said Richard Lafayette, M.D., F.A.C.P., Professor of Medicine, Nephrology and Director of the Glomerular Disease Center at Stanford University Medical Center, and a primary investigator for both ORIGIN 2b and ORIGIN 3.

“If approved, we believe that atacicept has the potential to advance the standard of care in IgAN as the first dual BAFF/APRIL inhibitor. We currently plan to submit a BLA for atacicept in IgAN to the FDA in the fourth quarter of this year, which may allow for US approval and commercial launch in 2026. We are grateful to the study participants, their families and caregivers, the study investigators and staff, our research partners, and the Vera team for their ongoing commitment and dedication to this important research,” said Marshall Fordyce, M.D., Founder and CEO of Vera Therapeutics. “Vera aspires to evolve the practice of kidney medicine with the hope that, one day, patients may no longer face a future of dialysis or transplantation. Vera is poised for potential commercial launch of atacicept in 2026 and to pursue development in additional indications in other autoimmune kidney diseases and beyond.”

“Patients with IgA nephropathy, as well as their families and care partners, suffer from clinical uncertainty and the horrible outcome of kidney failure. In addition to clinical signs and symptoms, IgAN has a devastating impact on quality of life and mental wellbeing. I’m thrilled with the progress that is being made in developing new treatments for patients,” said Bonnie Schneider, Director and Cofounder of the IgA Nephropathy Foundation.

ORIGIN 3 is an ongoing global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial of 431 adults with IgA nephropathy. Participants were randomized 1:1 to atacicept 150 mg, self-administered at home via once weekly subcutaneous injection, or placebo. The primary efficacy endpoint was the change in 24-hour UPCR compared to placebo at the 36-week interim analysis. The trial continues in a placebo-controlled blinded manner to evaluate the change in kidney function over two years as measured by eGFR and is expected to complete in 2027.

About Atacicept

Atacicept is an investigational recombinant fusion protein that contains the soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor that binds to the cytokines B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL). These cytokines are members of the tumor necrosis factor family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases, including IgAN, other autoimmune kidney diseases and lupus nephritis.

The ORIGIN Phase 2b clinical trial of atacicept in IgAN met its primary and key secondary endpoints, with statistically significant and clinically meaningful proteinuria reductions and stabilization of eGFR versus placebo through 36 weeks. The safety profile during the randomized period was comparable between atacicept and placebo. Through 96 weeks, atacicept demonstrated further improvements in Gd-IgA1, hematuria, and proteinuria, as well as stabilization of eGFR reflecting a profile consistent with that of the general population without IgAN.

Atacicept has received FDA Breakthrough Therapy Designation for the treatment of IgAN, which reflects the FDA’s determination that, based on an assessment of data from the ORIGIN Phase 2b clinical trial, atacicept may demonstrate substantial improvement on a clinically significant endpoint over available therapies for patients with IgAN. Vera believes atacicept is positioned for best-in-class potential, targeting B cells to reduce autoantibodies and having been administered to more than 1,500 patients in clinical trials across different indications.