Phase 3 ORIGIN Sets Stage for Atacicept in IgA Nephropathy, with Richard Lafayette, MD

Just days before the 62nd European Renal Association (ERA 2025) Congress, the nephrology community welcomed and celebrated new positive data for atacicept in IgA nephropathy (IgAN) in the form of topline results from the phase 3 ORIGIN trial.

Announced by Vera Therapeutics on June 02, 2025, topline results indicate the trial met its primary endpoint of reduction in proteinuria at week 36, with the atacicept group achieving a 46% reduction from baseline and a statistically significant 42% reduction compared to placebo at week 36.

“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 the trial’s lead investigator Richard Lafayette, professor of Medicine, Nephrology and director of the Glomerular Disease Center at Stanford University Medical Center.

According to Vera Therapeutics’ announcement of topline results, the company intends to meet with the US Food and Drug Administration (FDA) in the coming weeks to discuss these results and the regulatory pathway. According to the release, Vera Therapeutics intends to submit a Biologics License Application for accelerated approval to the FDA in 4Q 2025 and full 2-year data from the trial is expected in 2027.

An ongoing global, multicenter, randomized, double-blind, placebo-controlled phase 3 trial, ORIGIN enrolled 431 adults with IgAN and randomized them in a 1:1 ratio to atacicept 150 mg, self-administered at home via once weekly subcutaneous injection, or placebo therapy. Results announced by Vera Therapeutics indicate atacicept use was associated with 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 <.0001) at week 36. For other prespecified endpoints included in the trial, atacicept use was associated with results that were consistent with or better than those previously observed in the phase 2b ORIGIN trial.

Vera Therapeutics's announcement pointed out that the company is not sharing eGFR results at this time while the ORIGIN 3 placebo-controlled trial continues, which is a decision based on FDA guidance.

“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,” added Bonnie Schneider, Director and Cofounder of the IgA Nephropathy Foundation.

As part of our coverage of ERA 2025 Congress, we sat down with Lafayette to discuss how this latest data adds to our understanding of atacicept and its potential role in the management of IgAN if it were to receive FDA approval.

Relevant disclosures for Lafayette include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, Vera Therapeutics, and others.

References:

Vera Therapeutics. Vera Therapeutics Announces Atacicept Achieved 46% Proteinuria Reduction in ORIGIN Phase 3 Trial in Adults with IgA Nephropathy. Vera Therapeutics. Published June 2, 2025. Accessed June 5, 2025. https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-atacicept-achieved-46-proteinuria