Progress in IgAN and Future Innovations in Nephrology, with Richard Lafayette, MD

Only a few years ago, clinicians treating IgA nephropathy (IgAN) were limited to supportive care strategies such as blood pressure control and renin-angiotensin system blockade—approaches that, while beneficial, still left most patients at risk for progression to kidney failure. Now, the treatment landscape has dramatically shifted with the arrival of novel targeted therapies—and there’s more on the horizon.1

Most recently, the US Food and Drug Administration granted accelerated approval to Novartis’ atrasentan (Vanrafia), a once-daily, non-steroidal, oral treatment, for reducing proteinuria in adults with primary IgAN at risk of rapid disease progression based on a prespecified interim analysis of 36-week data from the ongoing phase 3 ALIGN trial. Of note, the decision marked the FDA’s first approval for a selective endothelin A receptor antagonist for reducing proteinuria in IgAN.1

Other recent developments in the IgAN treatment landscape include the full approval of Travere Therapeutics’ sparsentan (Filspari) and the accelerated approval of Novartis’ iptacopan (Fabhalta) in 2024, as well as the full approval of Calliditas Therapeutics’ budesonide (Tarpeyo) at the end of 2023.2,3,4

“Just 4 years ago, most patients would just be put on blood pressure control with agents to block angiotensin II,” Richard Lafayette, MD, a professor of medicine and director of the Glomerular Disease Center at Stanford University Medical Center, told HCPLive, noting that while there is a benefit to this approach, most patients would eventually require dialysis.

Similarly, he highlights shortcomings of more toxic immunosuppressive therapies that offered only temporary benefit, contrasting that with today’s growing armamentarium of targeted options.

“It's super exciting, because you can really have a menu of items. We want to think upstream and block the immune complexes if we can do that safely without immunologic and infectious complications, but downstream, being able to block those final determinants of complement and endothelin are really probably very helpful too,” he explained. “I think just having these different approaches, and more to come, is super exciting.”

Looking ahead to the rest of 2025, Lafayette points to even more innovations on the way. “There’s a whole group of anti-APRIL and BAFF agents being tested,” he says, citing promising early data suggesting these B-cell–modifying therapies could safely reduce proteinuria and stabilize kidney function. He also anticipates further progress in plasma cell–targeted approaches such as anti-CD38, as well as the application of targeted B-cell therapies in other glomerular diseases like membranous nephropathy and focal segmental glomerulosclerosis.

“I think the sun's really shining on the field. These are great days, but there's much more to come, and it's going to be a really exciting time,” Lafayette concluded.

Editors’ note: Relevant disclosures for Lafayette include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, and others.

References

1. Campbell P. Atrasentan (Vanrafia) Receives Accelerated Approval in IgA Nephropathy. HCPLive. April 2, 2025. Accessed April 11, 2025. https://www.hcplive.com/view/atrasentan-vanrafia-receives-accelerated-approval-in-igan

2. Brooks A. FDA Approves Travere Therapeutics’ Sparsentan to Slow Kidney Function Decline in Adult Primary IgAN. HCPLive. September 5, 2024. Accessed April 11, 2025. https://www.hcplive.com/view/fda-approves-travere-therapuetics-sparsentan-for-proteinuria-reduction-in-adult-primary-igan

3. Campbell P. Iptacopan Receives Accelerated Approval for Reducing Proteinuria in IgA Nephropathy. HCPLive. August 7, 2024. Accessed April 11, 2025. https://www.hcplive.com/view/iptacopan-receives-accelerated-approval-for-reducing-proteinuria-in-iga-nephropathy

4. Brooks A. FDA Awards Full Approval to Budesonide (Tarpeyo) in Treatment of IgA Nephropathy. HCPLive. December 20, 2023. Accessed April 11, 2025. https://www.hcplive.com/view/fda-awards-full-approval-to-budesonide-tarpeyo-in-treatment-of-iga-nephropathy