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Kidney Week 2025: ORIGIN 3 Sets the Stage for Atacicept in IgA Nephropathy
Phase 3 trial results reveal atacicept significantly reduces proteinuria in IgA nephropathy, paving the way for potential FDA approval in 2026.
Data from the 36-week analysis of the phase 3 ORIGIN 3 trial presented at the American Society of Nephrology (ASN) Kidney Week 2025 offers nephrology the greatest insight yet in the effects of atacicept in IgA nephropathy (IgAN).
Interim results of the ongoing, phase 3 trial suggest the dual BAFF/APRIL inhibitor was associated with a 45.7% reduction in urinary protein-to-creatinine ratio (UPCR) from baseline to 36 weeks, which equated to a between-group difference of 41.8 percentage points compared to placebo therapy.
“It's really, again, as good as it can be in terms of a result from the phase 3 [trial],” remarked principal investigator Richard Lafayette, MD, professor of Medicine and Nephrology as well as the director of the Glomerular Disease Center at Stanford University, in an episode of the Kidney Compass podcast. “Again, I'm allowed, as an independent person outside the company, to say I'm really excited and expect to see a wonderful GFR impact. For me, I want to see this drug available to our patients.”
The ASN Kidney Week presentation comes just more than 5 months after Vera Therapeutics announced the trial had met its primary endpoint in June 2025. In this announcement, Vera Therapeutics expressed the intent to submit a Biologics License Agreement for atacicept in IgAN to the FDA in Q4 2025, which would allow the possibility of a commercial launch in 2026.
On November 05, 2025, in a business update, Marshall Fordyce, MD, founder and CEO of Vera Therapeutics, stated the company remained on track for this BLA submission.
ORIGIN 3 is an ongoing global, multicenter, randomized, double-blind, placebo-controlled trial, including 431 adult patients with IgAN. 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 and is expected to conclude in 2027.
The interim analysis presented at Kidney Week 2025 and simultaneously published in the New England Journal of Medicine, offered insight into secondary outcomes of interest from the trial. These results included a marked reduction in Gd-IgA1 levels at 36 weeks, with a 68.3% decrease from baseline compared with 2.9% in the placebo group, and reductions were evident as early as week 4. By week 36, resolution of dipstick hematuria occurred in 81.0% of atacicept-treated patients versus 20.7% of those receiving placebo, and the UACR decreased by 47.3% with atacicept compared with 8.8% with placebo.
In the safety population (214 per group), median exposure was 34 weeks with atacicept and 31 weeks with placebo, with adverse events reported in 59.3% and 50.0% of patients, respectively. Injection-site reactions were more frequent with atacicept (19.2% vs 1.9%), while serious adverse events were less common (0.5% vs 5.1%), and no deaths occurred.
“These results build on earlier studies with similar findings and suggest that atacicept may preserve kidney function in patients with IgA nephropathy to a similar degree as in other individuals,” said Lafayette, in a press release from the ASN. “The phase 3 study is ongoing and will gather longer-term safety and efficacy data for atacicept in IgA nephropathy.”
