Following the US Food and Drug Administration’s (FDA) accelerated approval of atacicept (Trutakna) for adults with primary IgA nephropathy (IgAN) at risk for disease progression, Richard Lafayette, MD, FACP, discusses how BAFF/APRIL inhibition may reshape the treatment landscape for IgAN.

The approval was supported by data from the phase 3 ORIGIN 3 trial, in which atacicept reduced proteinuria by 42% compared with placebo at 36 weeks (P <.0001) and lowered galactose-deficient IgA1 (Gd-IgA1) levels by 68%.

Q&A: Atacicept and Upstream Immune Targeting in IgAN With Richard Lafayette, MD

HCPLive: Atacicept’s approval represents a major milestone in IgAN care. How do you see this therapy shaping the next era of disease management?

Lafayette: I think this is really an amazing event. Patients now have access to a medication that can completely retarget their disease course and can actually give them the promise of not slowing, but completely preserving, their kidney function.

Of course, that data is yet to be seen from the phase 3 study, but the phase 3 study results showing very dramatic improvements in proteinuria, hematuria, and control of galactose-deficient IgA to a similar, if not better, degree than what we saw in the phase 2 trial gives us great optimism that this will really control their disease in a meaningful way and give them that chance of true preservation of kidney function.

HCPLive: Atacicept targets both BAFF and APRIL, addressing key pathways involved in B-cell activation and IgAN pathogenesis. What does this approach reveal about our evolving understanding of the biology driving this disease?

Lafayette: I think there is a lot of potential pushback about the four-hit hypothesis and the underlying tenets of that, including the role of mucosal immune dysregulation and genetic predisposition.

I think the fact that a BAFF plus APRIL inhibitor is being so effective at managing these biomarkers of IgA nephropathy really lends credence to this being a disease of B-cell misregulation or dysregulation, and that both BAFF and APRIL have key elements in controlling the disease.

Atacicept itself can be successful at managing BAFF and APRIL and, in turn, reducing the aberrant immune response that underlies IgA nephropathy.

HCPLive: With the rapid expansion of disease-modifying therapies in IgAN, how should clinicians think about where atacicept fits within the broader treatment landscape?

Lafayette: I think we have very clear goals from KDIGO and other treatment guidelines to get the patient’s disease activity under control rapidly and effectively.

So if patients are not already near goal where they can be simply managed with supportive therapy, atacicept really represents a true way forward that is targeted, effective, well tolerated, and really should be a tool that we reach for in the vast majority of patients who have the need for intervention.

HCPLive: As clinicians begin incorporating atacicept into practice, which patients do you believe are most likely to derive the greatest benefit from this therapy?

Lafayette:I think any patient who is deemed at risk for progression. Again, those patients with more moderate disease can be stabilized with conservative therapy.

But any patient who fails reaching KDIGO guidelines of completely controlled proteinuria and no progression would be a fantastic candidate for atacicept, and hopefully will be treated in the near term.

HCPLive: The ongoing ORIGIN 3 trial will eventually provide important insight into long-term kidney outcomes. What questions do you hope these data will answer about atacicept’s potential to alter the trajectory of IgAN?

Lafayette: As I mentioned, we certainly have to wait for the GFR data for ORIGIN 3. Again, I’m confident that it will look similar to the phase 2b study, but seeing it is believing, and actually getting to that data will be really important.

We also hope it will shine light on the more long-term safety and tolerability of a once-weekly simple injection of atacicept, and that we’ll see, similar to the 9-month report, that the drug is well tolerated, that it’s safe, that it’s not associated with any excess infection, and most importantly, that the GFR truly is stable from baseline in patients who are experiencing these biomarker changes of improved proteinuria and hematuria.

HCPLive: Is there anything else you would like to highlight about atacicept and its role in IgAN?

Lafayette: Just to again go even deeper with the fact that this is the first real release of a drug that blocks both BAFF and APRIL, and that both cytokines have been legitimately linked to IgA nephropathy.

This really gives us the first opportunity to really control the source of the galactose-deficient IgA production and do it effectively.

Editor’s Note: Relevant disclosures for Lafayette include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, Vera Therapeutics, and others.

References

1. Vera Therapeutics. Vera Therapeutics Receives FDA Accelerated Approval for TRUTAKNA™ for Adult Patients with Primary IgA Nephropathy. July 7, 2026.

2. Lafayette R, Barbour SJ, Brenner RM, et al. A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy. N Engl J Med. Published online November 6, 2025. doi:10.1056/nejmoa2510198