Immunomodulatory

Atacicept

Research Reagent · Laboratory Use Only

Quick Answer

What does research show about atacicept for IgA nephropathy?

Atacicept is a TACI-Fc fusion protein that dually inhibits BAFF and APRIL, two cytokines that drive IgA nephropathy. The Phase 3 ORIGIN 3 trial (NEJM, 2026) showed a 45.7% reduction in proteinuria from baseline versus 6.8% for placebo at week 36. The FDA granted Vera Therapeutics accelerated approval for atacicept (Trutakna) on July 7, 2026, as the first therapy to dually target BAFF and APRIL in IgA nephropathy.

PMID41196369↗DOI10.1056/NEJMoa2510198↗⟳ Reconstitution Calculator
Scientific AbstractPMID 41196369 · 2026

Atacicept (marketed as Trutakna; atacicept-vymj) is a fully human recombinant TACI-Fc fusion protein — the extracellular BAFF/APRIL-binding domain of the transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI) receptor fused to a modified human IgG1 Fc domain — that dually neutralizes B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), two cytokines implicated as central drivers of IgA nephropathy (IgAN), the most common primary glomerulopathy worldwide. 001) at week 36. This built on earlier Phase 2 JANUS (NCT02808429, PMID 35967104) and Phase 2b ORIGIN (PMID 38552841) trials, which established dose-dependent proteinuria reduction and eGFR stabilization.

Based on the ORIGIN 3 interim data, the FDA granted Vera Therapeutics accelerated approval for Trutakna on July 7, 2026 — the first and only approved therapy that dually inhibits BAFF and APRIL — to reduce proteinuria in adults with primary IgAN at risk of disease progression. Continued approval is contingent on confirmatory verification of clinical benefit (kidney function preservation) in the ongoing trial.

Source:10.1056/NEJMoa2510198
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Atacicept?

Atacicept (marketed as Trutakna; atacicept-vymj) is a synthetic TACI-Fc fusion protein — a 313-amino-acid soluble receptor construct combining the BAFF/APRIL-binding extracellular domain of the TACI receptor with a modified human IgG1 Fc region (dimeric mass ~73.4 kDa). It is being investigated and, as of July 2026, is FDA-approved for IgA nephropathy (IgAN), a B-cell-origin kidney disease driven by mesangial deposition of IgA-containing immune complexes.

Mechanism of Action

Atacicept dually neutralizes two upstream immunoregulatory cytokines — B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) — that drive B-cell survival, maturation, and production of pathogenic galactose-deficient IgA1. By blocking both cytokines simultaneously (rather than either alone), atacicept sits further upstream in the IgAN pathogenic cascade than single-target agents.

Observed Clinical Results

  • Phase 2 JANUS (NCT02808429; PMID 35967104): Early dose-finding study in patients with persistent proteinuria despite maximal standard-of-care therapy.
  • Phase 2b ORIGIN (PMID 38552841; n=116): Mean urine protein-to-creatinine ratio (UPCR) reduced 31% from baseline (combined atacicept arms) versus 8% with placebo at week 24, and 34% versus a 2% increase with placebo at week 36; eGFR stabilized versus decline with placebo; galactose-deficient IgA1 fell 60% versus placebo.
  • Phase 3 ORIGIN 3 (NEJM, Feb 2026; PMID 41196369; NCT04716231; interim n=203): UPCR reduced 45.7% from baseline versus 6.8% with placebo at week 36 (between-group difference 41.8 percentage points, P<0.001).

Regulatory Status

FDA Approved (Accelerated Approval) — Vera Therapeutics' Trutakna (atacicept-vymj), a once-weekly 150 mg subcutaneous autoinjector, received FDA accelerated approval on July 7, 2026 to reduce proteinuria in adults with primary IgAN at risk of disease progression, based on the ORIGIN 3 interim analysis. It has not yet been established whether atacicept slows long-term kidney function decline; continued approval may depend on confirmatory trial results. Not a compounding-pharmacy peptide.

Clinical Research Parameters
2 trials3 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT02808429 ↗
COMPLETEDPhase IIn=16

Efficacy and Safety of Atacicept in IgA Nephropathy — JANUS

Randomized, placebo-controlled Phase 2 dose-finding study of atacicept (25 mg or 75 mg once weekly, subcutaneous) versus placebo in patients with IgA nephropathy and persistent proteinuria despite maximal standard-of-care therapy. 75% of patients completed at least 48 weeks of treatment; most treatment-emergent adverse events were mild or moderate. Established early safety and pharmacodynamic proof of concept for BAFF/APRIL dual inhibition in IgAN.

Study Interventions
Atacicept 25 mg, Atacicept 75 mg, Placebo
Primary Endpoints
Safety and tolerability; Change in serum galactose-deficient IgA1
Study Period
2016-08 → 2019-06
NCT04716231 ↗
ACTIVE NOT RECRUITINGPhase IIIn=431

A Study to Evaluate the Efficacy and Safety of Atacicept in Patients With IgA Nephropathy — ORIGIN 3

Global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial of once-weekly subcutaneous atacicept 150 mg versus placebo in adults with biopsy-proven IgA nephropathy. In a prespecified interim analysis of 203 patients, atacicept reduced 24-hour urine protein-to-creatinine ratio by 45.7% from baseline versus 6.8% with placebo at week 36 (between-group difference 41.8 percentage points, P<0.001). Adverse events were mostly mild-to-moderate, with a similar overall rate to placebo. Formed the primary basis of Vera Therapeutics' FDA accelerated approval (Trutakna) on July 7, 2026; the trial continues toward a confirmatory readout on kidney function outcomes.

Study Interventions
Atacicept (atacicept-vymj) 150 mg, Placebo
Primary Endpoints
Percent change from baseline in 24-hour urine protein-to-creatinine ratio at week 36
Study Period
2021-06 → 2027-06
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Atacicept is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 41196369) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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