Richard Lafayette, MD, is a professor of medicine and director of the Glomerular Disease Center at Stanford University Medical Center.

Richard Lafayette, MD

Welcome to Kidney Compass: Navigating Clinical Trials!

Kidney Compass: Lafayette and ORIGIN 3 at Kidney Week 2025

Kidney Compass: Navigating Clinical Trials

, hosts Brendon Neuen, MBBS, PHD, and Shikha Wadhwani, MD, MS, are joined by Ricahrd Lafayette, MD, from the floor at the 

American Society of Nephrology (ASN) Kidney Week 2025

 evaluating atacicept and how it adds to the totality of evidence supporting the use of the dual BAFF/APRIL inhibitor in IgA nephropathy (IgAN). 

Lafayette describes the moment as “predictably exciting,” noting that the phase 3 findings strongly mirror the promising signals seen previously in the ORIGIN phase 2 program.

The phase 2 trial, which evaluated weekly atacicept dosing, demonstrated a robust biologic impact with approximate reductions of 75% in galactose-deficient IgA1 and 50% in proteinuria at 96 weeks, hematuria resolution in most affected patients, and an annual eGFR decline of only ~0.6 mL/min/1.73 m², which Lafayette noted was far below the expected trajectory in this population. These data guided the design of ORIGIN 3, which enrolled biopsy-proven IgA nephropathy with >1 g/day of proteinuria, eGFR >30 mL/min/1.73 m², and maximally tolerated background therapy. More than half of the participants were also taking an SGLT2 inhibitor. 

Lafayette reports the 9-month primary outcome results aligned closely with phase 2. Atacicept achieved >45% reductions in proteinuria, compared with approximately 7% in the placebo group. Gd-IgA1 fell by approximately 75–80%, and hematuria resolved in most atacicept-treated patients with minimal change on placebo. Lafayette highlighted these effects were consistent across prespecified subgroups, including those on SGLT2 inhibitors.

Safety findings demonstrated there was no increase in infections or serious adverse events relative to placebo, aside from mild injection-site reactions. Lafayette pointed out, numerically, severe adverse events occurred more often in the placebo arm.

While regulatory restrictions prevent release of 9-month eGFR data, Lafayette notes the close resemblance to the phase 2 trajectory supports optimism for the upcoming 2-year readout. However, he emphasizes that atacicept-related biomarker improvements reverse when treatment stops, indicating that ongoing therapy may be necessary for sustained benefit.

The discussion concludes by situating atacicept within a rapidly expanding therapeutic landscape, including other B-cell–directed agents targeting APRIL alone. Head-to-head differences remain unknown, but atacicept’s dual BAFF/APRIL inhibition and consistent efficacy across optimized background therapy make it a compelling potential addition.

 include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, Vera Therapeutics, and others. Relevant disclosures for 

 include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Relevant disclosures for

include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others.

Lafayette R, Barbour SJ, Brenner RM, et al. 

ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN

. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.

Vera Therapeutics Announces Atacicept Achieved 46% Proteinuria Reduction in ORIGIN Phase 3 Trial in Adults with IgA Nephropathy. Vera Therapeutics, Inc. June 2, 2025. Accessed June 2, 2025. 

https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-atacicept-achieved-46-proteinuria

Podcasts

Discover groundbreaking insights from the ORIGIN 3 study on IgA nephropathy, showcasing promising results and future treatment possibilities.

Kidney Compass: Atacicept and ORIGIN 3 at Kidney Week 2025, with Richard Lafayette, MD

Counting down the biggest news from major medical meetings, it's the HCPLive Five!

HCPLive Five at European Renal Association (ERA) Congress 2025

European Renal Association (ERA) Congress

 is a medical conference bringing together world-renowned experts, researchers, and practitioners in nephrology. ERA Congress 2025 was hosted in Vienna, Austria, and saw more than 10,000 participants from  91 countries around the world, with a record 2835 abstract submissions. This year’s conference was centered around the theme “Game Changers in Nephrology” with the slogan “Beyond Nephrology,” boasting a comprehensive and innovative program exploring the latest advancements and transformative ideas in nephrology.

As part of HCPLive’s on-site coverage, the editorial team conducted expert interviews and reported on timely topics across therapeutic advances, pipeline updates, new renal clinical trial data, and more. In this edition of the HCPLive Five, the team highlights key conversations on pegcetacoplan in 

 and idiopathic immune-complex membranoproliferative glomerulonephritis (IC-MPGN), a trio of 

 drugs in clinical development, and the potential benefits of simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) in patients with 

Pegcetacoplan Sustains Proteinuria Reductions in C3G, IC-MPGN at 52 Weeks

Extended data from the phase 3 VALIANT trial were presented at ERA 2025 and support the sustained efficacy and safety of pegcetacoplan (Empaveli) in patients with C3G or IC-MPGN, including adolescents and adults with native or transplanted kidneys. The 52-week results show continued proteinuria reduction and eGFR stabilization in both treatment-naïve and crossover groups, reinforcing 26-week data presented at the American Society of Nephrology’s 2024 Scientific Sessions.

In this on-site interview at the meeting, Fadi Fakhouri, MD, PhD, co-lead principal investigator for the VALIANT study and a professor of nephrology at CHUV Lausanne, Switzerland, describes pegcetacoplan’s long-term potential in C3G and IC-MPGN and how the data presented at ERA could shift treatment strategies.

Understanding Zigakibart's Potential in IgA Nephropathy, with Jonathan Barratt, MD, PhD

100-week data from the phase 1/2 ADU-CL-19 trial presented at ERA suggest zigakibart, an APRIL inhibitor under development by Novartis, offers durable reductions in proteinuria and maintains a favorable safety profile in patients with IgAN. In the study, patients experienced a mean 60% reduction in proteinuria from baseline, with 55% achieving proteinuria below 500 mg and 31% below 300 mg, as described by Jonathan Barratt, MD, PhD, the Mayer Professor of Renal Medicine at the University of Leicester, in this interview. Additionally, serum IgA and pathogenic Gd-IgA1 levels dropped by 74%, building on earlier 52-week data showing reductions in IgA, IgM, and IgG of 67%, 78%, and 35%, respectively.

Kidney Compass: CONFIDENCE Trial at ERA 2025, with Rajiv Agarwal, MD, MS

Simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) in patients with CKD and type 2 diabetes was well-tolerated and resulted in significantly greater reductions in urinary albumin-to-creatinine ratio (UACR) than either agent alone, according to results from the CONFIDENCE trial. During ERA, Kidney Compass host Brendon Neuen, MBBS, PhD, a senior research fellow with the George Institute for Global Health and the director of the Kidney Trials Unit with Royal North Shore Hospital, held a discussion with trial investigators Rajiv Agarwal, MD, Professor Emeritus at Indiana University School of Medicine, about the study results and what they mean for CKD management landscape in real-world settings.

Phase 3 ORIGIN Sets Stage for Atacicept in IgA Nephropathy, with Richard Lafayette, MD

Just days before the ERA 2025, the nephrology community welcomed and celebrated new positive data for atacicept in IgAN in the form of topline results from the phase 3 ORIGIN trial. Announced by Vera Therapeutics on June 02, 2025, the data indicate the trial met its primary endpoint of reduction in proteinuria at week 36, with the atacicept group achieving a 46% reduction from baseline and a statistically significant 42% reduction compared to placebo at week 36.

’s coverage of ERA, we sat down with Lafayette to discuss how this latest data adds to our understanding of atacicept and its potential role in the management of IgAN if it were to receive FDA approval.

Kidney Compass: Sibeprenlimab and the VISIONARY Trial, with Vlado Perkovic, MBBS, PhD, at ERA 2025

, hosts Brendon Neuen, MBBS, PHD, and Shikha Wadhwani, MD, MS, are joined by Vlado Perkovic, MBBS, PhD, dean and scientia professor of Medicine at UNSW Sydney, as he dives into one of the meeting’s most anticipated releases—

. Less than 2 weeks prior to the presentation, Otsuka Pharmaceutical Co. announced the US Food and Drug Administration had granted priority review for their BLA and the application has been given a target action date of November 28, 2025.

These 5 represent only some of the data the 

 team covered at this year's meeting! Check out more KOL insight and our full conference coverage on our 

Videos

From new data for potential IgAN treatments to the use of combination initiation therapy for type 2 diabetes and CKD, here are 5 key updates from the annual meeting.

62nd European Renal Association (ERA 2025) Congress

, the nephrology community welcomed and celebrated new positive data for atacicept in 

 in the form of topline results from the phase 3 ORIGIN trial.

Announced by Vera Therapeutics on June 02, 2025, topline results indicate the trial met its primary endpoint of reduction in proteinuria at week 36, with the atacicept group achieving a 46% reduction from baseline and a statistically significant 42% reduction compared to placebo at week 36.

“ORIGIN 3 is the first Phase 3 clinical trial in IgAN to demonstrate this magnitude of UPCR reduction compared to placebo at week 36. These results convincingly demonstrate the impact of atacicept to reduce proteinuria,” said the trial’s lead investigator Richard Lafayette, professor of Medicine, Nephrology and director of the Glomerular Disease Center at Stanford University Medical Center.

According to Vera Therapeutics’ announcement of topline results, the company intends to meet with the US Food and Drug Administration (FDA) in the coming weeks to discuss these results and the regulatory pathway. According to the release, Vera Therapeutics intends to submit a Biologics License Application for accelerated approval to the FDA in 4Q 2025 and full 2-year data from the trial is expected in 2027.

An ongoing global, multicenter, randomized, double-blind, placebo-controlled phase 3 trial, ORIGIN enrolled 431 adults with IgAN and randomized them in a 1:1 ratio to atacicept 150 mg, self-administered at home via once weekly subcutaneous injection, or placebo therapy. Results announced by Vera Therapeutics indicate atacicept use was associated with a 46% reduction from baseline in proteinuria as measured by 24-hour urine protein-to-creatinine ratio (UPCR), with a statistically significant and clinically meaningful 42% reduction in UPCR compared to placebo (

<.0001) at week 36. For other prespecified endpoints included in the trial, atacicept use was associated with results that were consistent with or better than those previously observed in the phase 2b ORIGIN trial.

Vera Therapeutics's announcement pointed out that the company is not sharing eGFR results at this time while the ORIGIN 3 placebo-controlled trial continues, which is a decision based on FDA guidance.

“Patients with IgA nephropathy, as well as their families and care partners, suffer from clinical uncertainty and the horrible outcome of kidney failure. In addition to clinical signs and symptoms, IgAN has a devastating impact on quality of life and mental wellbeing. I’m thrilled with the progress that is being made in developing new treatments for patients,” added Bonnie Schneider, Director and Cofounder of the IgA Nephropathy Foundation.

As part of our coverage of ERA 2025 Congress, we sat down with Lafayette to discuss how this latest data adds to our understanding of atacicept and its potential role in the management of IgAN if it were to receive FDA approval.

Relevant disclosures for Lafayette include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, Vera Therapeutics, and others.

Vera Therapeutics. Vera Therapeutics Announces Atacicept Achieved 46% Proteinuria Reduction in ORIGIN Phase 3 Trial in Adults with IgA Nephropathy. Vera Therapeutics. Published June 2, 2025. Accessed June 5, 2025. 

Richard Lafeyette, MD, discusses his reaction to the phase 3 ORIGIN topline results and what it means for IgAN. 

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

Only a few years ago, clinicians treating 

 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.

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.

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.

“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 

, 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.

Campbell P. Atrasentan (Vanrafia) Receives Accelerated Approval in IgA Nephropathy. 

. April 2, 2025. Accessed April 11, 2025. 

https://www.hcplive.com/view/atrasentan-vanrafia-receives-accelerated-approval-in-igan

Brooks A. FDA Approves Travere Therapeutics’ Sparsentan to Slow Kidney Function Decline in Adult Primary IgAN. 

. September 5, 2024. Accessed April 11, 2025. 

https://www.hcplive.com/view/fda-approves-travere-therapuetics-sparsentan-for-proteinuria-reduction-in-adult-primary-igan

Campbell P. Iptacopan Receives Accelerated Approval for Reducing Proteinuria in IgA Nephropathy. 

. August 7, 2024. Accessed April 11, 2025. 

https://www.hcplive.com/view/iptacopan-receives-accelerated-approval-for-reducing-proteinuria-in-iga-nephropathy

Brooks A. FDA Awards Full Approval to Budesonide (Tarpeyo) in Treatment of IgA Nephropathy. 

. December 20, 2023. Accessed April 11, 2025. 

https://www.hcplive.com/view/fda-awards-full-approval-to-budesonide-tarpeyo-in-treatment-of-iga-nephropathy

Lafayette reflects on recent therapeutic advances in IgA nephropathy and looks ahead to other renal pipeline developments he’s looking forward to in 2025.

Richard Lafayette, MD

Articles