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Abstract: FR-OR034

Efficacy and Safety of Atrasentan in Patients (Pts) with IgAN from East (E) Asia: Phase 3 ALIGN Interim Data

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Zhang, Hong, Peking University First Hospital, Beijing, China
  • Barratt, Jonathan, The Mayer IgA Nephropathy Laboratories, University of Leicester, Leicester, United Kingdom
  • Heerspink, Hiddo Jan L., Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Jardine, Meg, National Health and Medical Research Council Clinical Trials Center, University of Sydney, Sydney, New South Wales, Australia
  • Lafayette, Richard A., Stanford University, Stanford, California, United States
  • Kohan, Donald E., Division of Nephrology, University of Utah Heath, Salt Lake City, Utah, United States
  • Levin, Adeera, The University of British Columbia, Vancouver, British Columbia, Canada
  • Twiston Davies, Helen, Novartis Pharmaceuticals, London, United Kingdom
  • Patel, Ankit B., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States
  • Morris, Elena, 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
  • Liew, Adrian, Mount Elizabeth Novena Hospital, Singapore, Singapore
Background

In the ALIGN interim analysis (IA), atrasentan, a highly selective, potent ETA receptor antagonist, reduced 24-hour urine protein–creatinine ratio (24h-UPCR) by 36.1% vs placebo (pbo) at Week (W) 36 and had a favorable safety profile (NCT04573478). Atrasentan (VANRAFIA®) received US FDA accelerated approval for proteinuria reduction in adults with primary IgAN at risk of rapid disease progression. IgAN is most prevalent in Asian pts; we report ALIGN IA results for pts from E Asia.

Methods

ALIGN is an ongoing, double-blind, Phase III trial in adults with IgAN and 24-hour total urine protein ≥1 g/day on optimized supportive care. Pts were randomized to receive atrasentan 0.75 mg/day or pbo. An IA occurred when 270 pts completed or discontinued before the W36 visit. Exploratory efficacy and safety analyses were conducted for pts from E Asia (n=120; China mainland 45.0%, Japan 18.3%, South Korea 26.7%, other 10.0%; atrasentan n=59, pbo n=61) and all pts of Asian race (n=154).

Results

Baseline demographics were balanced between arms. In pts from E Asia, atrasentan reduced 24h-UPCR at W36 by 41.1% (95% CI 25.4, 53.5; Figure) vs pbo. In pts with baseline 24h-UPCR ≥1.5 g/g or <1.5 g/g, 24h-UPCR reduction at W36 vs pbo was 47.1% (95% CI 23.0, 63.6) and 37.5% (95% CI 14.2, 54.5), respectively (Figure). Treatment-emergent AEs occurred in 88.1% of pts on atrasentan and 88.5% on pbo, and led to treatment discontinuation in 3.4% and 3.3% of pts, respectively. Data were consistent for all pts of Asian race.

Conclusion

Atrasentan was well tolerated and led to a clinically meaningful 24h-UPCR reduction vs pbo in pts from E Asia, supporting the potential of atrasentan as a foundational treatment for Asian pts with IgAN.

Funding

  • Commercial Support – Novartis

Digital Object Identifier (DOI)