Atacicept Slows IgAN Decline to Physiologic Rate, With Sayna Norouzi, MD

Two years of data from the phase 3 ORIGIN 3 trial show atacicept (Trutakna) stabilized kidney function and lowered the risk of kidney disease progression compared with placebo in adults with primary IgA nephropathy (IgAN).¹ The final efficacy analysis adds long-term kidney outcome data for a therapy currently approved only on the basis of proteinuria reduction.¹

"The ultimate goal, and the ultimate question my patients ask, is whether this medication is going to preserve my kidney function," said ORIGIN 3 study investigator Sayna Norouzi, MD, assistant professor of medicine and clinical nephrologist at Loma Linda University Medical Center, director of the Glomerular and Polycystic Kidney Diseases Clinics, and chief education officer of GlomCon, in an interview with HCPLive. "Whenever we talk about kidney disease, patients talk about dialysis or transplant, and this is something they want to prevent."

Through 104 weeks, atacicept was associated with a slower annualized decline in estimated glomerular filtration rate (eGFR) than placebo (−0.6 vs −5.6 mL/min/1.73 m² per year; treatment effect, 5.0; 95% CI, 3.6–6.5; P < .0001) and a 76% lower risk of a composite kidney disease progression event (hazard ratio, 0.24; 95% CI, 0.12–0.48; P < .0001), according to a September 15, 2026, release from Vera Therapeutics.¹,² According to Vera, the eGFR slope aligns with the KDIGO treatment goal of reducing kidney function decline to the physiologic rate (<1 mL/min/1.73 m² per year).¹

ORIGIN 3 trial design: once-weekly atacicept vs placebo in IgAN

ORIGIN 3 (NCT04716231) is a global, multicenter, randomized, double-blind, placebo-controlled phase 3 trial in adults with primary IgAN at risk for disease progression. Participants were randomized 1:1 to self-administered subcutaneous atacicept 150 mg once weekly or placebo for a 104-week double-blind period, followed by a 52-week open-label extension.³

The primary endpoint, change in urine protein to creatinine ratio (UPCR) at 36 weeks, was assessed in an interim analysis and published in The New England Journal of Medicine.³ Those results supported the US Food and Drug Administration (FDA) accelerated approval of atacicept to reduce proteinuria in July 2026.⁴ The key secondary endpoint, eGFR change through 104 weeks, was evaluated in the full study population, with 428 patients in the final analysis set.¹

Atacicept stabilized eGFR and prevented dialysis, transplant events at 2 years

At 52 weeks, mean eGFR change from baseline was −0.1 mL/min/1.73 m² (95% CI, −1.4 to 1.2) with atacicept vs −5.7 mL/min/1.73 m² (95% CI, −7.0 to −4.4) with placebo (treatment effect, 5.6; 95% CI, 3.7–7.5; P < .0001).¹

Atacicept met all prespecified endpoints in the final efficacy analysis. Through 104 weeks, 11 patients receiving atacicept experienced a composite kidney disease progression event, compared with 38 patients receiving placebo. No patients receiving atacicept experienced dialysis for ≥30 days, kidney transplantation, or death, compared with 8 patients receiving placebo.¹

"If a medication can show us preservation of kidney function, that's huge for us, and that's huge for patients as well," Norouzi said. "It's one area where there is a lot of alignment between what we want and what our patients want."

Atacicept also achieved statistically significant reductions in the hierarchically tested endpoints of proteinuria, galactose-deficient IgA1 (Gd-IgA1), and hematuria.¹

"Prevention of kidney failure or kidney-related death is the ultimate goal. We now have evidence suggesting that Trutakna may help patients avoid dialysis, transplantation, or kidney-related death over the long term," Richard Lafayette, MD, professor of medicine and director of the Glomerular Disease Center at Stanford University Medical Center and a principal investigator for ORIGIN 3, said in a statement.¹

Atacicept safety: infection rates similar to placebo

Rates of overall adverse events and of infections or infestations were similar between the atacicept and placebo groups. No opportunistic infections or clinically relevant hypogammaglobulinemia occurred.¹ Across clinical trials, the most common adverse reactions with atacicept vs placebo were infections (32% vs 28%) and local administration reactions (30% vs 5%).¹

Supplemental BLA for full approval of atacicept planned for Q4 2026

Vera plans to submit a supplemental Biologics License Application (sBLA) to the FDA in the fourth quarter of 2026, seeking full approval, and will present detailed results at an upcoming scientific congress.¹ Atacicept remains approved under accelerated approval based on proteinuria reduction. Its long-term effect on kidney function decline has not yet been formally established in the label.¹

"The numbers are looking good, and again, it's bringing a lot of hope for us and for patients," Norouzi said.

References

1. Vera Therapeutics. Vera Therapeutics announces Trutakna (atacicept-vymj) stabilized eGFR and prevented kidney disease progression through two years in ORIGIN 3 final efficacy analysis in IgA nephropathy. Published September 15, 2026. Accessed September 29, 2026. https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-trutaknatm-atacicept-vymj-stabilized

2. Hillenbrand A. Atacicept cuts IgAN progression risk 76% in ORIGIN 3 final data. HCPLive. Published September 15, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/atacicept-cuts-igan-progression-risk-76-in-origin-3-final-data

3. Lafayette R, Barbour SJ, Brenner RM, et al. A phase 3 trial of atacicept in patients with IgA nephropathy. N Engl J Med. 2026;394(7):647-657. doi:10.1056/NEJMoa2510198

4. Hillenbrand A. FDA approves atacicept (Trutakna) for IgA nephropathy. HCPLive. Published July 7, 2026. Accessed September 29, 2026. https://www.hcplive.com/view/fda-approves-atacicept-trutakna-for-iga-nephropathy