Abstract: FR-PO0827
Renin-Angiotensin System Inhibitor (RASi) Use and Atrasentan in IgAN: Post Hoc Analysis from the ALIGN Trial
Session Information
- Glomerular Clinical Trials: From Data to Impact
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Lafayette, Richard A., Stanford University, Stanford, California, United States
- Barratt, Jonathan, The Mayer IgA Nephropathy Laboratories, University of Leicester, Leicester, United Kingdom
- Jardine, Meg, National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
- Kohan, Donald E., Division of Nephrology, University of Utah Health, Salt Lake City, Utah, United States
- Levin, Adeera, The University of British Columbia, Vancouver, British Columbia, Canada
- Liew, Adrian, Mount Elizabeth Novena Hospital, Singapore, Singapore
- Zhang, Hong, Peking University First Hospital, Beijing, China
- Twiston Davies, Helen, Novartis Pharmaceuticals, London, United Kingdom
- Patel, Ankit B., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States
- Kearbey, Jeffrey, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States
- Ansari, Soudeh, Novartis Pharmaceuticals Corporation, Cambridge, Massachusetts, United States
- Dahlke, Marion, Novartis Pharma AG, Basel, Switzerland
- Heerspink, Hiddo Jan L., Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Background
Atrasentan, a highly selective ETA receptor antagonist, significantly reduced proteinuria vs placebo (pbo) in patients (pts) with IgAN in the ALIGN (NCT04573478) interim analysis. Atrasentan (VANRAFIA®) received US FDA accelerated approval for proteinuria reduction in adults with primary IgAN at risk of rapid disease progression. Given global variability in RASi regimens, a post hoc analysis assessed the ALIGN Week 36 primary endpoint data by baseline (BL) RASi class and dose.
Methods
ALIGN is an ongoing, Phase III, randomized, double-blind study of atrasentan 0.75 mg/day vs pbo in adults with IgAN on stable, maximally tolerated RASi. Change from BL in 24-hour urine protein–creatinine ratio (24h-UPCR) at Week 36 was assessed by RASi class and by percentage of the maximum labeled dose (MLD) of RASi (≤50% or >50%) prescribed at BL.
Results
Pts received two-thirds (69.0%) of MLD RASi on average. Of 270 pts, 54.4% received ≤50% MLD RASi and 41.1% received >50% MLD RASi. At BL, 71.1% and 27.4% of pts, respectively, were on an angiotensin II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEi); 23 distinct ARBs and 10 distinct ACEis were prescribed. At Week 36, a 24h-UPCR reduction of 39.3% (95% CI 30.3, 47.0) was seen in the atrasentan arm for pts on ≤50% MLD RASi and a reduction of 37.5% (95% CI 27.4, 46.2) was seen in the atrasentan arm in pts on >50% MLD RASi (Figure). 24h-UPCR reductions of 36.8% (95% CI 28.9, 43.7) and 41.5% (95% CI 29.1, 51.7) were seen in the atrasentan arm for pts on ARB and ACEi, respectively.
Conclusion
Atrasentan led to clinically meaningful proteinuria reduction regardless of BL RASi class (ARB or ACEi) and dose. These data support the potential for atrasentan to be seamlessly added onto a variety of existing RASi treatment and dose regimens. The results add to the available data for atrasentan, which has the potential to be a foundational therapy in IgAN.
Funding
- Commercial Support – Novartis