Kidney Week

Abstract: SA-OR076

Povetacicept for Treatment of IgA Nephropathy: RAINIER Phase 3 Interim Efficacy and Safety Analysis (IA)

Session Information

• Late-Breaking Research Orals: Pediatrics, Genetics, and Glomerular Diseases
  October 24, 2026 | Location: Four Seasons Ballroom 2, Convention Center
  Abstract Time: 05:06 PM - 05:18 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Lafayette, Richard A., Stanford University School of Medicine, Stanford, California, United States

Richard A. Lafayette, MD

• Zhang, Hong, Peking University First Hospital, Beijing, China

Hong Zhang, MD, PhD

• Han, Seung Hyeok, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Seung Hyeok Han, MD, PhD

• Suzuki, Yusuke, Juntendo Daigaku Igakubu Daigakuin Igaku Kenkyuka, Tokyo, Japan

Yusuke Suzuki, MD, PhD

• Tumlin, James A., NephroNet LLC, Lawrenceville, Georgia, United States

James A. Tumlin, MD, FASN

• Chacko, Bobby, John Hunter Hospital, New Lambton Heights, New South Wales, Australia

Bobby Chacko, MD, MBBS, FASN

• Noronha, Irene L., Universidade de Sao Paulo, São Paulo, SP, Brazil

Irene L. Noronha, MD, PhD

• Madan, Arvind, Central Florida Kidney Specialists, Orlando, Florida, United States

Arvind Madan, MD, MBBS, FASN

• Duivenvoorden, Raphael, Radboud universitair medisch centrum, Nijmegen, GE, Netherlands

Raphael Duivenvoorden, MD, PhD

• Azzi, Jamil R., Brigham and Women's Hospital, Boston, Massachusetts, United States

Jamil R. Azzi, MD, PhD

• Nester, Carla M., The University of Iowa Stead Family Children's Hospital, Iowa City, Iowa, United States

Carla M. Nester, MD, MS, FASN

• Dong, Cassie, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Cassie Dong, PhD

• Ahluwalia, Neil, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Neil Ahluwalia, MD

• Li, Jiahua, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Jiahua Li, MD, PhD

• Bozic, Carmen, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Carmen Bozic, MD

• Egbuna, Ogo I., Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Ogo I. Egbuna, MD, MS, MSc, FASN

• Wong, Muh Geot, The University of Sydney School of Life and Environmental Sciences, Sydney, New South Wales, Australia

Muh Geot Wong, MBBS, PhD

• Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom

Jonathan Barratt, MBChB, PhD

Background

BAFF and APRIL play distinct roles in B cell proliferation, differentiation, function, and survival. In IgAN, elevated expression of both BAFF and APRIL drives B cell activation, differentiation, and proliferation, promoting overproduction of Gd-IgA1 and anti-Gd-IgA1 autoantibodies that form pathogenic immune complexes. Povetacicept is an enhanced, variant TACI–crystallizable fragment fusion therapeutic engineered for dual BAFF/APRIL inhibition with robust binding affinity and potency, favorable pharmacokinetics, broad tissue distribution, and administered subcutaneous (SC) Q4W with a small volume, thin needle autoinjector.

Methods

The RAINIER Phase 3, randomized, double-blind, placebo (pbo)-controlled trial is ongoing in adults with biopsy-proven IgAN: 557 participants on optimized standard-of-care were randomized to povetacicept 80 mg (N=371) or pbo (N=186) SC Q4W (main cohort). Prespecified efficacy IA included 199 participants (N=131 povetacicept; N=68 pbo). The IA primary endpoint was change from baseline in 24hr-UPCR and secondary endpoints were change from baseline in Gd-IgA1 and proportion of participants with hematuria resolution, all at Week (Wk)36.

Results

Povetacicept significantly reduced 24hr-UPCR (-52.0%) compared to pbo (-4.3%) at Wk36, with pbo-adjusted treatment effect of 49.8% (95% CI: 39.2% to 58.6%; P<0.0001). The treatment effect on change from baseline in 24hr-UPCR at Wk36 was consistent across all subgroups evaluated. More participants (42.2%) on povetacicept achieved 24hr-UPCR <0.5 g/g at Wk36 compared to those on pbo (6.2%). Gd-IgA1 was significantly reduced with povetacicept (-77.4%) compared to an increase with pbo (+9.1%), with pbo-adjusted effect of 79.3% (95% CI: 75.9% to 82.2%; P<0.0001). Among those with hematuria at baseline, povetacicept led to significant hematuria resolution (85.1%) compared to pbo (23.4%), with a pbo-adjusted treatment effect of 61.7% (95% CI: 44.9% to 78.4%; P<0.0001). Povetacicept was generally safe and well tolerated with a similar incidence of adverse events (75.0% vs 78.4%) and serious adverse events (3.0% vs 4.3%) to pbo.

Conclusion

Povetacicept results in rapid, sustained, and clinically and statistically significant reductions in proteinuria, Gd-IgA1, and hematuria compared to pbo at Wk36 and was generally safe and well tolerated, indicating povetacicept is a disease-modifying therapy for adults with IgAN.

Funding

• Commercial Support – Vertex Pharmaceuticals Inc