Treatment with atacicept slowed and stabilized the decline in the estimated glomerular filtration rate (eGFR) as compared with placebo, in adult patients with biopsy-confirmed IgA nephropathy, according to the results of the phase 3 Origin 3 clinical trial.
Statistically significant, concordant improvements were observed across all prespecified efficacy endpoints, and with a favorable safety profile.
“What we've shown here is that it is achievable to get the rate of loss of kidney function back to what we see in healthy individuals in a high-risk population,” said study author Jonathan Barratt, MBChB, Ph.D., FRCP, the Mayer Professor of Renal Medicine at the University of Leicester, UK. “You can see at two years that placebo-adjusted change was 11.1 mils per minute, and the difference in the annualized DGFR slope, using all the available GFR data, was 5 mLs per minute per year, what would you expect to see on healthy adults.”
Treatment with atacicept produced an annualized (eGFR) slope of –0.6 mL/min/1.73 m² per year vs –5.6 with placebo. It also reduced the risk of composite kidney disease progression by 76% by week 104, explained Barratt.
The findings were presented at American Society of Nephrology (ASN) Kidney Week 2026 and simultaneously published in The New England Journal of Medicine.
Atacicept is a native human transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI)–Fc fusion protein. It inhibits the cytokines B-cell activating factor (BAFF, also known as B-lymphocyte stimulator, or BLyS) and a proliferation-inducing ligand (APRIL) which are involved in the pathogenesis of IgA nephropathy. Atacicept is the first agent targeting both B-cell activating factor and a proliferation-inducing ligand (APRIL). The overlapping roles of BAFF and APRIL in activating B cells support the potential for Atacicept as a disease-modifying therapy.
The FDA granted accelerated approval to atacicept in July 2026, following a prespecified interim analysis of the ORIGIN 3 trial. In the interim analysis, participants achieved a 46% reduction from baseline in proteinuria compared to about 7% in the placebo group at 36 weeks.
The ORIGIN 3 is a multinational, Phase 3, randomized, double-blind, placebo-controlled trial comprised of 428 patients with IgA nephropathy who were randomized to receive either atacicept 150 mg or placebo. Prespecified efficacy endpoints included placebo-adjusted change from baseline in eGFR at Week 52, annualized eGFR slope through Week 104, and composite kidney-disease progression through Week 104. Safety was also assessed.
“The goal of treatment is that we must get the rate of loss of kidney function down to what we see in healthy individuals, less than one mL per minute per year,” said Barratt, “If we have any hope of preventing kidney failure in the lifetime of people living with IgA nephropathy. And what we've seen from the many new CKD therapies is that they simply cannot achieve that in this patient population.”
At week 52, the mean change in the eGFR was −0.11 mL/min/1.73 m² of body-surface area with atacicept compared with −5.69 mL/min/1.73 m² for patients receiving placebo (mean difference, 5.58 mL/min/1.73 m²; P<0.001). Composite kidney-disease progression occurred in 11 patients (5.1%) in the atacicept group vs 38 (17.8%) in the placebo group (hazard ratio, 0.24; P<0.001).
"If you hadn't exposed them to an atacicept, they would have lost 12 mL of kidney function in 2 years, which is perhaps the highest rate of loss of kidney function we've seen in any IgA nephropathy trial in a placebo group," Barratt said
None of the patients receiving atacicept progressed to dialysis, transplantation, or death vs 7 in the placebo group. Overall, adverse events were similar in both groups; 160 for atacicept (74.8%) vs 167 for placebo (78.0%) in the placebo group.
“It has a well tolerated and favorable safety profile,” said Barratt. "We are now actively transitioning all those placebo patients onto drug because that's the reason and the driver for why we wanted to look at the data earlier and not expose placebo patients to just standard-of-care therapy.”
These data will be submitted to the FDA next year for full approval, he added.
Abstract: TH-OR109 Opening Plenary; The ORIGIN 3 Trial: Atacicept in IgA Nephropathy
The ORIGIN 3 Trial was supported by Vera Therapeutics, Inc. Barratt disclosed relationships with Alexion Pharmaceuticals, Argenx, AstraZeneca, Biogen, Biohaven Pharmaceuticals, Calliditas, F. Hoffmann-La Roche, Novartis, Omeros Corporation, Otsuka Pharmaceutical, Takeda Pharmaceuticals, Travere Therapeutics, Vera Therapeutics, and Vertex Pharmaceuticals.
