Trutakna Reduces Proteinuria in Adults With Primary IgAN

IgA nephropathy (IgAN) is an autoimmune condition characterized by the abnormal deposition of galactose-deficient IgA1 (Gd-IgA1) antibody immune complexes in the kidneys, leading to inflammation, proteinuria, and reduced overall kidney function.^1,2 IgAN is the most common cause of immune-mediated glomerular disease worldwide and has an annual incidence of 1.9 to 2.2 per 100,000 persons in the US.¹ With a main goal of treatment to reduce the rate of kidney function loss and restore it to its physiological state, therapy is aimed at decreasing pathogenic IgA production and immune complex formation, as well as managing the effects of existing nephron loss.³

In July 2026, the FDA granted accelerated approval of atacicept-vymj (Trutakna) for the reduction of proteinuria in adults with primary IgAN at risk for disease progression.⁴ Atacicept-vymj works by binding and inhibiting both B-lymphocyte stimulator (BLyS) and A Proliferation Inducing Ligand (APRIL), thereby decreasing their signaling pathways and subsequently lowering the production of serum Gd-IgA1.⁴ Atacicept-vymj is the first and only approved therapy that targets both of the important pathophysiological drivers of Gd-IgA1 production, BLyS and APRIL.^2,4

READ MORE: Emerging Data Show Potential Risk of Autoimmune Diseases With GLP-1 Use

Efficacy

The efficacy of atacicept-vymj was evaluated during the interim analysis of a multicenter, double-blind, randomized, placebo-controlled trial (ORIGIN 3, NCT04716231; n = 203). The trial included adults with primary IgAN who had a proteinuria level greater than or equal to 1.0 g/day, an estimated glomerular filtration rate greater than or equal to 30 mL/min/1.73 m², and at least 12 weeks of treatment with a stable dose of a maximally tolerated renin–angiotensin system inhibitor. Patients were randomly assigned 1:1 to receive a subcutaneous dose of 150 mg of atacicept-vymj once weekly or a matching placebo. The primary outcome evaluated the percentage change in the 24-hour urine protein-to-creatinine ratio (UPCR) from baseline to week 36. At week 36, a 45.7% reduction was seen in the UPCR in the atacicept-vymj group and a 6.8% reduction in the placebo group, with a geometric mean between-group difference of 41.8 percentage points (95% CI, 28.9-52.3; P < .001).^4,5 

Safety

The safety of atacicept-vymj was evaluated in the ORIGIN 3 trial, which included 428 adult patients. Adverse events were reported in 59.3% of the atacicept-vymj group and 50% of the placebo group, most of which were mild or moderate and resolved without interruption or discontinuation of treatment. The most common adverse reactions (≥5%) reported in the atacicept-vymj group included infections (32%), with the most common being upper respiratory tract infections (12%), injection-site reactions (19%), and injection-site erythema (6%).^4,5

It is contraindicated in patients with serious hypersensitivity to atacicept-vymj or any of its excipients. Given its immunosuppressant nature, atacicept-vymj can increase the risk of serious infections; therefore, it should be delayed in patients with active infections until the infection resolves or is adequately treated. Live vaccines should be avoided during use and for 30 days before initiation of atacicept-vymj, as the safety of coadministration has not yet been established. Additionally, the mechanism of action of atacicept-vymj suggests it may cause immunosuppression in an infant exposed in utero. Although fetal risk and use in pregnancy have not been established, this potential clinical impact should be considered. ⁴

Dosing

Atacicept-vymj is available as a 150 mg/mL single-dose prefilled autoinjector. Atacicept-vymj can be administered at home by the patient or their caregiver as a 150 mg subcutaneous injection once weekly. The injection site should alternate with each administration and can include either the abdomen or thigh. If a dose is missed, it should be given as soon as possible, and the once-weekly regimen should be resumed 1 week after the missed dose.⁴ The duration of treatment has not been established, but the indication will likely be lifelong.³ The autoinjector should be stored in the refrigerator and brought to room temperature 15 to 30 minutes prior to injection. It may be kept at room temperature for up to 72 hours, after which it must be discarded.⁴

READ MORE: Autoimmune Disease Resource Center

REFERENCES

1. Stoneman S, Teh JW, O’Shaughnessy MM. IgA nephropathy in adults: a review. JAMA. 2026;335(9):799-813. doi:10.1001/jama.2025.25020

2. Cheung CK, Barratt J, Liew A, Zhang H, Tesar V, Lafayette R. The role of BAFF and APRIL in IgA nephropathy: pathogenic mechanisms and targeted therapies. Front Nephrol. 2024;3:1346769. doi:10.3389/fneph.2023.1346769

3. Floege J, Barratt J, Cook HT, et al. Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Kidney Int. 2025;108(4):548-554. doi:10.1016/j.kint.2025.04.003

4. Trutakna. Prescribing information. Vera Therapeutics Inc; 2026. Accessed September 16, 2026. https://webfiles.veratx.com/docs/TRUTAKNA_Prescribing_Information.pdf

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