FDA grants accelerated approval to Vera’s Trutakna, first dual BAFF/APRIL inhibitor for IgA nephropathy

Edited by Robert McTiernan··3 min read

The US FDA has granted accelerated approval to Trutakna (atacicept-vymj) for reducing proteinuria in adults with primary IgA nephropathy (IgAN) at risk of disease progression — marking the first approval of a dual BAFF and APRIL inhibitor in any indication. California-based Vera Therapeutics (Nasdaq: VERA) positions the therapy as a mechanistically distinct addition to an increasingly crowded IgAN landscape, where several agents have reached approval over the past four years.

The approval is based on a surrogate endpoint — reduction in proteinuria — rather than demonstrated preservation of kidney function. As a condition of accelerated approval, continued authorization is contingent on confirmatory evidence from the ongoing ORIGIN 3 trial evaluating estimated glomerular filtration rate (eGFR) decline, with results anticipated in Q3 2026. Trutakna is administered as a 150 mg subcutaneous injection once weekly via autoinjector, self-administered by patients at home.

Atacicept-vymj is a soluble recombinant fusion protein incorporating the extracellular domain of the TACI receptor, enabling it to simultaneously neutralize both BAFF and APRIL — two cytokines that drive B-cell activation and the production of galactose-deficient IgA1 (Gd-IgA1), the pathogenic antibody central to IgAN. By blocking both ligands, the molecule targets the immunological cascade upstream of glomerular immune complex deposition.

The approval rests on a prespecified interim analysis of ORIGIN 3 (NCT04716231), a global, multicenter, randomized, double-blind, placebo-controlled Phase III trial. Among the first 203 participants who received at least one dose, those treated with Trutakna demonstrated a 46% reduction from baseline in 24-hour urine protein-to-creatinine ratio (UPCR) at 36 weeks, representing a statistically significant 42% reduction versus placebo (p<0.0001). A 68% reduction in Gd-IgA1 was also reported as a secondary endpoint, though without multiplicity adjustment. The safety profile was broadly consistent with the drug's immunosuppressive mechanism: infections occurred in 32% of Trutakna-treated patients versus 28% on placebo, and local administration reactions in 30% versus 5%.

The IgAN treatment landscape has expanded considerably since Tarpeyo (budesonide delayed-release capsules), developed by Calliditas Therapeutics, received the first FDA approval in the indication in December 2021 — also under accelerated approval based on proteinuria reduction. Sparsentan (Filspari), a dual endothelin and angiotensin receptor antagonist developed by Travere Therapeutics, followed a similar regulatory path and carries identical approved indication language. Trutakna’s differentiation lies in its immunologic mechanism: rather than modulating hemodynamic or mucosal pathways, it directly suppresses the B-cell cytokine axis considered central to IgAN pathogenesis.

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The most direct mechanistic competition comes from povetacicept, a dual BAFF/APRIL inhibitor in development at Vertex Pharmaceuticals. As previously reported, Vertex has reported Phase III data for povetacicept in IgAN, and the FDA has set a November decision date for that agent — meaning two drugs targeting the same cytokine pair could hold approval in the same indication within months of each other. The competitive pressure extends further: Novartis has reported Phase III data for iptacopan (Vanrafia/Fabhalta) in IgAN via a complement pathway mechanism, broadening the mechanistic diversity of the field.

For Vera Therapeutics, Trutakna represents the company’s first commercial product and the culmination of a development program built on rights licensed from Merck KGaA in November 2020. Atacicept was originally discovered by ZymoGenetics and co-developed with Merck Serono from 2001; Vera acquired global rights under an agreement that included 10% equity to Merck KGaA and up to €605 million in potential milestones. The IgAN pivot — away from the lupus indications previously explored under Merck Serono — proved central to Vera’s strategy, with the ORIGIN program generating the clinical evidence that ultimately supported the BLA.

The eGFR readout from ORIGIN 3 expected in Q3 2026 will determine whether the accelerated approval converts to full approval and, more broadly, whether proteinuria reduction at 36 weeks reliably predicts long-term kidney function preservation for this class of agent — a question with implications beyond Trutakna alone.

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