Atacicept Achieves Endpoints in Phase 3 ORIGIN Trial for IgA Nephropathy

Atacicept, an investigational recombinant fusion protein for the treatment of immunoglobulin A nephropathy (IgAN), has met its primary endpoint of a statistically significant reduction in urine protein-to-creatinine ratio (UCPR) compared to placebo in the ORIGIN Phase 3 trial.1

Announced by Vera Therapeutics, Inc. on June 02, 2025, ORIGIN results demonstrate patients treated with atacicept achieved a 46% reduction from baseline proteinuria, as measured by 24-hour UPCR, which corresponded with a 42% reduction in UCPR compared to placebo (P <.0001) at week 36. Vera Therapeutics plans to submit a Biologics License Application in the fourth quarter of 2025, opening the possibility for the drug’s commercial launch in 2026.1

“ORIGIN 3 is the first phase 3 clinical trial in IgAN to demonstrate this magnitude of UPCR reduction compared to placebo at week 36,” said Richard Lafayette, MD, professor of Medicine and Nephrology as well as the director of the Glomerular Disease Center at Stanford University Medical Center. “These results convincingly demonstrate the impact of atacicept to reduce proteinuria.”1

Atacicept 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). Both cytokines are part of the tumor necrosis factor family, which promote survival of B-cells and autoantibody production associated with IgAN, lupus nephritis, autoimmune kidney diseases, and a variety of other autoimmune diseases.1

The phase 2b ORIGIN study reached its endpoint after just 24 weeks, exhibiting a statistically significant UPCR reduction versus placebo.2

The phase 3 ORIGIN trial is an ongoing global, multicenter, randomized, double-blind, placebo-controlled trial, including 431 adult patients with IgA nephropathy. Investigators randomized participants 1:1 to atacicept 150 mg, self-administered once weekly at home through subcutaneous injection, or placebo. The trial will continue to monitor changes in kidney function over 2 years following treatment; it is expected to conclude in 2027.1

Vera Therapeutics plans to submit these results to the US Food and Drug Administration (FDA) over the next few weeks. The medication has already received the FDA Breakthrough Therapy Designation, indicating the organization’s belief that atacicept may demonstrate substantial improvement on a clinically significant endpoint over available therapies for patients with IgAN.1

“If approved, we believe that atacicept has the potential to advance the standard of care in IgAN as the first dual BAFF/APRIL inhibitor,” said Marshall Fordyce, MD, founder and chief executive officer 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 of transplantation.”1

References:

1. Vera Therapeutics Announces Atacicept Achieved 46% Proteinuria Reduction in ORIGIN Phase 3 Trial in Adults with IgA Nephropathy. Vera Therapeutics, Inc. June 2, 2025. Accessed June 2, 2025. https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-atacicept-achieved-46-proteinuria

2. Brooks, A. Atacicept Shows Disease-Modifying Potential in IgAN, Linked to Hematuria Resolution. HCPLive. June 11, 2024. Accessed June 2, 2025. https://www.hcplive.com/view/atacicept-shows-disease-modifying-potential-in-igan-linked-to-hematuria-resolution