TRUTAKNA stabilized kidney function and reduced kidney disease progression risk in the Phase 3 ORIGIN 3 trial in adults with IgA nephropathy.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
Vera Therapeutics announced that TRUTAKNA (atacicept-vymj) met all prespecified endpoints in the final efficacy analysis of the Phase 3 ORIGIN 3 trial (NCT04716231) in adults with primary IgA nephropathy (IgAN) at risk of disease progression. The final analysis included 428 patients and showed near-stable kidney function with TRUTAKNA compared with a substantial decline with placebo, along with a significant reduction in the risk of composite kidney disease progression. TRUTAKNA also maintained a favorable safety profile generally comparable to placebo. The company plans to submit a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2026 seeking full approval.
IgA Nephropathy and the Need for Disease-Modifying Treatment
IgA nephropathy is a serious, progressive, immune-mediated kidney disease and a leading cause of chronic kidney disease and kidney failure worldwide. Approximately 2.5 adults per 100,000 people worldwide are diagnosed with IgAN each year, most often between 30 and 40 years of age. The disease can cause irreversible kidney damage and may ultimately require dialysis or kidney transplantation. At least 50% of patients may progress to kidney failure or death within 10 to 20 years of diagnosis.
TRUTAKNA is the first and only FDA-approved inhibitor of both B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL). It is a soluble recombinant fusion protein containing the human TACI receptor that binds BAFF and APRIL, cytokines involved in B-cell activation and IgAN pathophysiology. TRUTAKNA is administered subcutaneously at 150 mg once weekly using a prefilled autoinjector.
ORIGIN 3 Final Analysis: Kidney Function and Disease Progression Results
At 52 weeks, mean eGFR change from baseline was -0.1 mL/min/1.73m² with TRUTAKNA compared with -5.7 mL/min/1.73m² with placebo, representing a treatment effect of 5.6 mL/min/1.73m² (95% CI, 3.7-7.5; p<0.0001).
Through 104 weeks, the annualized eGFR slope was -0.6 mL/min/1.73m²/year with TRUTAKNA versus -5.6 mL/min/1.73m²/year with placebo, corresponding to a treatment effect of 5.0 mL/min/1.73m²/year (95% CI, 3.6-6.5; p<0.0001). These findings align with the KDIGO treatment goal of slowing kidney function decline to the physiologic rate of less than 1 mL/min/1.73m²/year.
The composite kidney disease progression endpoint occurred in 11 patients receiving TRUTAKNA versus 38 receiving placebo, corresponding to a hazard ratio of 0.24 (95% CI, 0.12-0.48; p<0.0001), representing a 76% reduction in risk. No patients receiving TRUTAKNA experienced dialysis for at least 30 days, transplantation, or death through 104 weeks, compared with eight patients receiving placebo. TRUTAKNA also significantly reduced proteinuria, galactose-deficient IgA1 (Gd-IgA1), and hematuria.
Safety Profile Comparable to Placebo
TRUTAKNA was generally well tolerated, with overall adverse events and infections or infestations occurring at similar rates to placebo. No opportunistic infections or clinically relevant hypogammaglobulinemia were reported.
The FDA prescribing information identifies infection risk as an important warning and reports infections in 32% of TRUTAKNA patients versus 28% with placebo. Common adverse reactions include upper respiratory tract infection, injection-site reaction, and injection-site erythema. The prescribing information recommends assessing patients for active infection and completing age-appropriate immunizations before treatment.
Regulatory Path and Early Commercial Momentum
TRUTAKNA received FDA accelerated approval in July 2026 based on its ability to reduce proteinuria. The approval was contingent on verification of clinical benefit, making the ORIGIN 3 final analysis important for demonstrating effects on kidney function and disease progression.
Vera plans to submit a supplemental BLA in the fourth quarter of 2026 seeking full approval, with potential FDA action in 2027. Since launch, the company has generated more than 350 patient start forms in the first ten weeks and has reported paid claims and encouraging initial payer policies.
Reference
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, Vera Therapeutics, 15 September 2026
Atacicept in Subjects With IgA Nephropathy (ORIGIN 3), ClinicalTrials.gov ID NCT04716231
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.