> ## Content Index
> Fetch the complete content index at: https://bioweek.com/llms.txt
> Use this file to discover other available public pages before exploring further.

# Atacicept Matches Normal Kidney Aging in Two-Year IgA Nephropathy Trial
- URL: https://bioweek.com/atacicept-matches-normal-kidney-aging-in-two-year-iga-nephropathy-trial/
- Published: 2026-09-16T05:03:53.000Z
- Updated: 2026-09-16T05:03:53.000Z
- Description: Two-year ORIGIN 3 data show weekly atacicept flattened eGFR decline to 0.6 mL/min per year and cut kidney-progression events by 76 percent, with no dialysis or transplants on drug.
- Author: BioWeek
- Tags: Pipeline, Science

Vera Therapeutics [announced](https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-trutaknatm-atacicept-vymj-stabilized?ref=bioweek.com) that TRUTAKNA (atacicept-vymj) held kidney function near the pace of healthy aging over two years in IgA nephropathy, and sharply reduced the events that usually send patients toward dialysis. In the Phase 3 ORIGIN 3 [trial](https://clinicaltrials.gov/study/NCT04716231?ref=bioweek.com), the annualized eGFR slope on weekly 150 mg subcutaneous atacicept was -0.6 mL/min/1.73m2 per year, versus -5.6 on placebo. Composite kidney-progression events fell 76 percent. No patient on drug needed dialysis or a transplant; eight on placebo did.

Those figures, [published](https://www.nejm.org/doi/full/10.1056/NEJMoa2510198?ref=bioweek.com) in The New England Journal of Medicine, matter because IgA nephropathy is the most common primary glomerular disease worldwide, diagnosed in about 2.5 per 100,000 adults each year, typically in young adults. More than half progress to end-stage kidney disease or death within 10 to 20 years. The biology starts upstream: overproduction of galactose-deficient IgA1 (Gd-IgA1) and autoantibodies that form immune complexes and lodge in the glomerular mesangium. Most approved IgAN drugs still work downstream of that synthesis.

### A slope that meets the KDIGO aging bar

ORIGIN 3 randomized and treated 428 adults with biopsy-proven IgAN at high risk of progression, 214 to atacicept and 214 to placebo. Mean baseline eGFR was 64 mL/min/1.73m2\. Mean 24-hour urine protein-to-creatinine ratio was 1.6 g/g. Every patient was on a stable renin-angiotensin system inhibitor; 61 percent (263 patients) were also on an SGLT2 inhibitor, so the control arm already reflected contemporary background care.

At week 52, mean eGFR change was -0.1 mL/min/1.73m2 (95% CI -1.4 to 1.2) on atacicept versus -5.7 (95% CI -7.0 to -4.4) on placebo, a placebo-adjusted preservation of 5.6 mL/min/1.73m2 (p < 0.0001). By week 104 the annualized slope was -0.6 (95% CI -1.6 to 0.4) versus -5.6 (95% CI -6.6 to -4.6), a treatment benefit of 5.0 mL/min/1.73m2 per year (p < 0.0001).

The 2025 KDIGO [guideline](https://kdigo.org/guidelines/igan-igav/?ref=bioweek.com) for IgA nephropathy sets a treatment target of slowing decline to the physiologic rate of less than 1.0 mL/min/1.73m2 per year. Atacicept’s -0.6 slope sits inside that band. Placebo, even on RASi plus widespread SGLT2 inhibition, did not.

### Hard events, not just a surrogate

Proteinuria has been the regulatory on-ramp in IgAN. ORIGIN 3 now supplies the harder composite: death, kidney transplant, chronic dialysis of at least 30 days, eGFR below 15 mL/min/1.73m2, or a sustained 30 percent or greater eGFR drop. That endpoint hit 11 patients (5 percent) on TRUTAKNA versus 38 (18 percent) on placebo (hazard ratio 0.24, 95% CI 0.12 to 0.48, p < 0.0001). Dialysis, transplant, or death: zero versus eight over 104 weeks.

The biomarker package lines up with that clinical separation. Placebo-adjusted UPCR fell 42 percent (a 46 percent reduction on drug, p < 0.0001). Gd-IgA1 dropped 68 percent versus 3 percent on placebo (p < 0.0001). Hematuria resolved in 81 percent versus 21 percent (odds ratio 19.1, p < 0.0001). Those are the circulating and urinary fingerprints of the disease process, not just filtration noise.

### Dual cytokine blockade versus the rest of the class

Atacicept is a recombinant soluble TACI-Fc fusion protein that binds BAFF (Kd 106 pM) and APRIL (Kd 33 pM). The 150 mg weekly autoinjector is 1 mL. Dual neutralization hits both cytokines that drive B-cell survival and the plasma-cell output of Gd-IgA1, which is the mechanistic case Vera is making against the rest of the IgAN shelf.

Calliditas’s Tarpeyo is a targeted-release budesonide aimed at gut-associated lymphoid tissue. Travere’s Filspari dual-blocks the endothelin A and angiotensin II type 1 receptors. Novartis’s Fabhalta inhibits complement Factor B. Those are downstream pressure valves: steroids, hemodynamics, complement amplification. They do not shut off the autoantibody factory.

Single-target anti-APRIL antibodies, Otsuka’s sibeprenlimab and Novartis’s zigakibart, come closer to the same axis. The ORIGIN 3 argument is that APRIL alone is incomplete because BAFF can still support pathogenic B cells. The safety data are the counterweight to that dual hit. Overall adverse events were 75 percent versus 78 percent on placebo. Serious adverse events were 7 percent versus 15 percent. Discontinuations for adverse events were 2 percent versus 10 percent. Infections were 51 percent versus 52 percent, with serious infections 3 percent versus 4 percent. There were no opportunistic infections, no clinically relevant hypogammaglobulinemia, and no deaths on drug. Injection-site reactions were the price of the autoinjector: 25 percent versus 7 percent.

That profile is the commercial bet. Dual BAFF/APRIL suppression can look immunosuppressive on a slide. In this 428-patient, two-year dataset it did not produce a systemic immunodeficiency signal that would scare nephrologists off a chronic weekly biologic.

### From accelerated approval to a full label

The FDA granted accelerated approval in July 2026 on 36-week proteinuria. Vera says more than 350 patient start forms were logged in the first 10 weeks of launch. An sBLA is planned for the fourth quarter of 2026, aiming at traditional approval in 2027\. Two-year eGFR slope and a 76 percent cut in composite kidney events are the package that conversion will rest on.

The remaining questions are practical. ORIGIN 3 enrolled high-risk, biopsy-proven adults already optimized on RASi, many of them on SGLT2 inhibitors. How atacicept stacks against, or on top of, Filspari, Fabhalta, and the anti-APRIL monoclonal antibodies in routine care is still a sequencing problem, not a settled algorithm. Durability past two years, real-world infection rates, and whether the aging-rate slope holds once patients leave a trial protocol will decide whether TRUTAKNA becomes background therapy or a specialist add-on. For now, the two-year evidence is unusually clean: kidney function that tracks normal aging, fewer progression events, and no one on drug reaching dialysis.