FDA Grants Accelerated Approval to TRUTAKNA for IgA Nephropathy

The U.S. Food and Drug Administration has granted accelerated approval to TRUTAKNA (atacicept-vymj) to reduce proteinuria in adults with primary IgA nephropathy (IgAN) at risk for disease progression. Developed by Vera Therapeutics, TRUTAKNA is the first and only approved therapy to simultaneously inhibit B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), targeting key immune pathways underlying IgAN. The approval is supported by a prespecified interim analysis of the ongoing Phase 3 ORIGIN trial, in which TRUTAKNA produced statistically significant reductions in proteinuria, an established surrogate marker of long-term kidney outcomes.

Phase 3 ORIGIN trial demonstrated clinically meaningful efficacy

The ongoing global, multicenter, randomized, double-blind, placebo-controlled ORIGIN Phase 3 trial (NCT04716231) enrolled adults with primary IgAN receiving optimized standard-of-care therapy. Participants were randomized 1:1 to receive TRUTAKNA 150 mg or placebo through a once-weekly subcutaneous autoinjector for home administration.

At the prespecified 36-week interim analysis involving the first 203 treated participants, TRUTAKNA reduced the 24-hour urine protein-to-creatinine ratio (UPCR) by 46% from baseline and achieved a 42% greater reduction than placebo (p<0.0001). Benefits remained consistent across prespecified patient subgroups. Treatment also reduced circulating galactose-deficient IgA1 (Gd-IgA1) by 68%, supporting its targeted effect on the disease’s underlying immunopathology.

Targeting the underlying biology of IgAN

IgAN is the most common primary glomerular disease worldwide and a leading cause of chronic kidney disease and kidney failure. The disease is driven by galactose-deficient IgA1 immune complexes that accumulate in the kidney glomeruli, causing chronic inflammation and progressive renal damage despite optimized supportive therapy.

TRUTAKNA is a recombinant fusion protein containing the transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor, enabling simultaneous inhibition of BAFF and APRIL. By blocking both cytokines, the therapy reduces pathogenic Gd-IgA1 production and immune complex formation, targeting the immune process responsible for disease progression. TRUTAKNA is administered as a 150 mg once-weekly subcutaneous injection using a patient self-administered autoinjector.

Safety profile supported approval

Safety was evaluated in 428 patients who received at least one dose of TRUTAKNA or placebo. The therapy was generally well tolerated, with infections (32% vs. 28%) and local administration reactions (30% vs. 5%) reported more frequently than placebo. Upper respiratory tract infection, injection-site reaction, and injection-site erythema were the most common adverse events. No serious or opportunistic infections, hypogammaglobulinemia, or clinically significant effects of anti-drug antibodies were observed, and most adverse events were mild to moderate.

Experts highlight a new treatment approach

Marshall Fordyce, MD, Founder and Chief Executive Officer of Vera Therapeutics, said the approval establishes the first dual BAFF/APRIL inhibitor for IgAN and marks an important step toward addressing the disease’s underlying immune drivers.

Richard Lafayette, MD, Professor of Medicine and Director of the Glomerular Disease Center at Stanford University Medical Center and a principal investigator in the ORIGIN program, said dual BAFF/APRIL inhibition offers nephrologists a new treatment strategy directed at the core biology of IgAN.

Bonnie Schneider, Director and Co-Founder of the IgAN Foundation, said the approval brings renewed hope to patients and families seeking additional treatment options.

Confirmatory trial continues

The FDA granted accelerated approval based on proteinuria reduction, and long-term preservation of kidney function has not yet been established. Continued approval will depend on confirmation of clinical benefit in the ongoing blinded ORIGIN trial evaluating changes in estimated glomerular filtration rate (eGFR). Results are expected in Q3 2026 and could support conversion to traditional FDA approval.

What This Means for Patients

TRUTAKNA offers a new treatment option for adults with IgA nephropathy who are at risk of worsening kidney disease. Unlike standard treatments that mainly control symptoms, this medicine works on the underlying cause of the disease to reduce harmful immune activity. It is given as a once-weekly injection that patients can administer at home. While the treatment has been shown to reduce excess protein in the urine, ongoing research will determine whether it also protect kidney function over the long term.

Reference

Vera Therapeutics Receives FDA Accelerated Approval for TRUTAKNA™ for Adult Patients with Primary IgA Nephropathy | Vera Therapeutics, Inc.