FDA Grants Accelerated Approval to Trutakna as First BAFF and APRIL Inhibitor for IgA Nephropathy

Vera Therapeutics announced today that the FDA has granted accelerated approval to atacicept-vymj (brand name Trutakna) for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression.¹ The approval makes Trutakna the first and only therapy in the US that targets both B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), the two key upstream cytokines responsible for driving the B-cell-mediated autoimmune cascade at the source of IgAN pathophysiology.¹ The decision represents a significant milestone in a rapidly evolving targeted biologic treatment field for IgAN, where multiple mechanisms are now advancing toward clinical use after decades in which patients had few disease-modifying options.

What is IgA nephropathy and why has it been difficult to treat?

IgAN is the most common primary glomerulonephritis worldwide — a serious, progressive, immune-mediated kidney disease in which abnormal, galactose-deficient IgA1 (Gd-IgA1) antibodies accumulate in the glomerular mesangium, triggering autoantibody formation, immune complex deposition, inflammation, and progressive kidney injury.² The disease most commonly presents between 30 and 40 years of age and carries a substantial long-term burden: at least 50% of patients may progress to kidney failure or death within 10 to 20 years of diagnosis, with approximately 160,000 patients estimated to be affected in the US and 2.5 per 100,000 adults newly diagnosed globally each year.¹,³

Until recently, management centered on supportive measures — renin-angiotensin-aldosterone system (RAAS) inhibition, blood pressure control, and SGLT2 inhibitors — without meaningfully targeting the underlying immunological mechanism.⁴ The FDA approval of sparsentan (Filspari) in 2023 for proteinuria reduction in IgAN introduced the first targeted therapy, but sparsentan is a small-molecule dual endothelin/angiotensin receptor antagonist rather than a biologic, and it does not address the upstream B-cell-mediated pathogenesis. Trutakna now offers the first approved therapy in the US that directly inhibits the cytokines responsible for Gd-IgA1 overproduction.

How does Trutakna work?

Trutakna is a soluble recombinant fusion protein containing the human transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor fused to an Fc domain.¹ The TACI receptor naturally binds both BAFF and APRIL — two TNF-family cytokines that activate B cells to produce Gd-IgA1 and its autoantibodies, the initiating step of IgAN pathogenesis.² By acting as a soluble decoy receptor, atacicept intercepts and neutralizes both cytokines simultaneously, blocking B-cell activation and plasma cell antibody secretion upstream of immune complex formation.²

The dual BAFF/APRIL inhibition strategy is mechanistically distinct from anti-APRIL-only approaches (such as sibeprenlimab) and from complement inhibitors and endothelin/angiotensin receptor antagonists — placing Trutakna at a unique position in the evolving IgAN treatment algorithm as the only approved agent that directly intervenes at the B-cell level.⁵ Trutakna is self-administered subcutaneously once weekly via autoinjector, enabling at-home dosing without infusion center visits.¹

"I frequently hear from IgAN patients who are uncertain about what this disease may mean for their future, reflecting the historic high risk of poor outcomes with standard therapies," said Richard Lafayette, MD, FACP, Professor of Medicine, Nephrology and Director of the Glomerular Disease Center at Stanford University Medical Center, and a principal investigator in the ORIGIN clinical program. "Trutakna offers patients and their nephrologists an exciting new treatment advancement that inhibits both BAFF and APRIL, the two key cytokines that act on B cells, which are at the source of IgAN pathophysiology."¹

What did the ORIGIN 3 trial show?

The accelerated approval is based on a prespecified interim analysis of the ongoing ORIGIN 3 trial (NCT04716231), a global, multicenter, randomized, double-blind, placebo-controlled phase 3 study enrolling adults with IgAN.¹ Participants were randomized 1:1 to Trutakna 150 mg or placebo, self-administered at home via once-weekly subcutaneous injection.

In the first 203 participants who received at least one dose, Trutakna achieved a 46% reduction from baseline in 24-hour urine protein-to-creatinine ratio (UPCR), with a statistically significant and clinically meaningful 42% reduction compared to placebo (p<0.0001) at 36 weeks.¹ The proteinuria benefit was consistent across all prespecified subgroups including age, sex, race, region, baseline proteinuria, baseline eGFR, and baseline SGLT2 inhibitor use.¹ Participants treated with Trutakna also experienced a 68% reduction in Gd-IgA1 — a secondary endpoint directly reflecting the upstream mechanism and a biomarker of reduced disease activity.¹

Trutakna was generally well tolerated. The most common adverse reactions were infections (32% vs 28% with placebo) and local administration reactions (30% vs 5%), the majority of which were mild or moderate and resolved without treatment interruption. No serious, severe, or opportunistic infections or hypogammaglobulinemia were observed in Trutakna-treated patients.¹

The ORIGIN 3 trial continues in a placebo-controlled, blinded manner to evaluate the effect of Trutakna on kidney function decline as measured by eGFR — the data required for potential conversion to full traditional approval — with results anticipated in Q3 2026.¹ The phase 3 NEJM publication of the full ORIGIN 3 dataset was published simultaneously with the approval.⁶

What does the approval mean for the IgAN treatment field?

The accelerated approval of Trutakna arrives as the IgAN treatment field undergoes a generational transformation. The KDIGO 2025 Clinical Practice Guidelines for IgAN now recommend proteinuria reduction as a central treatment goal and recognize it as a validated surrogate marker of reduced risk of kidney function decline — the regulatory and clinical framework that supports the accelerated approval pathway Vera used for Trutakna.⁷ Multiple mechanistically distinct agents are now approved or in late-stage development for IgAN, including sparsentan (dual endothelin/angiotensin receptor antagonist), iptacopan (complement factor B inhibitor, approved 2024), and sibeprenlimab (anti-APRIL monoclonal antibody, in phase 3), creating a treatment arena in which combination regimens targeting complementary pathways may eventually become standard of care.⁵

"The approval of Trutakna as the first and only BAFF and APRIL inhibitor for IgAN marks an important milestone and we believe it has the potential to meaningfully transform the treatment of this serious disease," said Marshall Fordyce, MD, founder and ceo of Vera Therapeutics in a press release. "We are grateful to the patients, investigators, study teams and regulators whose efforts made this achievement possible."¹

Vera is also developing Trutakna in additional autoimmune kidney indications including membranous nephropathy and focal segmental glomerulosclerosis under the PIONEER study protocol, as well as VT-109, a next-generation BAFF/APRIL fusion protein licensed from Stanford University with potentially broader B-cell-mediated disease coverage.¹ Eligible commercially insured patients may pay as little as $0 out of pocket through the Trutakna TRU SUPPORT patient assistance program.¹

References

1. Vera Therapeutics Receives FDA Accelerated Approval for TRUTAKNA™ for Adult Patients with Primary IgA Nephropathy. (2026 Jul 7). GlobeNewswire. https://www.globenewswire.com/news-release/2026/07/07/3323532/0/en/vera-therapeutics-receives-fda-accelerated-approval-for-trutakna-for-adult-patients-with-primary-iga-nephropathy.html
2. Cheung CK, Barratt J, Liew A, Zhang H, Tesar V, Lafayette R. (2024 Feb). The role of BAFF and APRIL in IgA nephropathy: pathogenic mechanisms and targeted therapies. Front Nephrol. https://pubmed.ncbi.nlm.nih.gov/38362118/
3. Pitcher D, Braddon F, Hendry B, et al. (2023 Jun 1). Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. https://pubmed.ncbi.nlm.nih.gov/37055195/
4. Xu Y, Mo Y, Xu Y. (2026 Jan 26). Advances in novel biologics targeting BAFF/APRIL in the treatment of IgA nephropathy. Cells. https://pubmed.ncbi.nlm.nih.gov/41677607/
5. Sharma I, Panta R. (2025 Dec 22). Emerging therapies in IgA nephropathy: from APRIL and BAFF inhibitors to precision medicine. Cureus. https://www.cureus.com/articles/443169-emerging-therapies-in-iga-nephropathy-from-a-proliferation-inducing-ligand-april-and-b-cell-activating-factor-baff-inhibitors-to-precision-medicine#!/
6. Lafayette R, Barbour SJ, Brenner RM, et al. (2025 Nov 6). A phase 3 trial of atacicept in patients with IgA nephropathy. N Engl J Med. https://www.nejm.org/doi/full/10.1056/NEJMoa2510198
7. Floege J, Barratt J, Cook HT, et al. (2025 Oct). Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of IgAN and IgAV. Kidney Int. https://pubmed.ncbi.nlm.nih.gov/40975525/
8. Atacicept in Subjects With IgA Nephropathy (ORIGIN 3). CenterWatch. https://www.centerwatch.com/clinical-trials/listings/NCT04716231/atacicept-in-subjects-with-iga-nephropathy