Kidney Week

Abstract: FR-PO855

AFFINITY Study: 1-Year Results of Atrasentan in IgA Nephropathy

Session Information

• IgA Nephropathy: Clinical, Outcomes, and Therapeutics
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

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

Jonathan Barratt, MBChB, PhD

• Kim, Sung Gyun, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)

Sung Gyun Kim, MD, PhD

• Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States

Lesley Ann Inker, MD, MS

• Packham, David K., Melbourne Renal Research Group, Reservoir, Victoria, Australia

David K. Packham, MD, PhD

• Ranganathan, Dwarakanathan, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Dwarakanathan Ranganathan, MD, FASN

• Rheault, Michelle N., University of Minnesota Twin Cities Division of Pediatric Nephrology, Minneapolis, Minnesota, United States

Michelle N. Rheault, MD

• Vishnepolsky, Mark, Kidney Specialists of Southern Nevada, Las Vegas, Nevada, United States

Mark Vishnepolsky, MD, MS, MBA, FASN

• Brahmbhatt, Yasmin G., Chinook Therapeutics Inc, A Novartis Company, Seattle, Washington, United States

Yasmin G. Brahmbhatt, MD, FASN

• Wang, Yi, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States

Yi Wang, PhD

• Beckett, Valeria, Chinook Therapeutics Inc, A Novartis Company, Seattle, Washington, United States

Valeria Beckett

• Han, Seung Hyeok, Severance Hospital, Seodaemun-gu, Seoul, Korea (the Republic of)

Seung Hyeok Han, MD, PhD

Background

Endothelin A (ET_A) receptor activation drives kidney dysregulation in glomerular diseases (GD). Atrasentan, a potent, selective ET_A receptor antagonist, has been shown to reduce proteinuria and may preserve kidney function in patients (pts) with IgAN and other GD. AFFINITY is a Phase 2, open-label basket study evaluating the efficacy and safety of atrasentan in pts with GD. We present results from the IgAN cohort through 1 year (52 wks) of treatment.

Methods

The IgAN cohort included adults with biopsy-proven IgAN; eGFR ≥30 mL/min/1.73m², UPCR ≥0.5 g/g and <1.0 g/g (first morning void), and on max. tolerated/stable RASi for ≥12 wks. Pts took 0.75 mg oral atrasentan daily for 52 wks. The primary endpoint was change in 24h UPCR from baseline (BL) to Wk 12.

Results

The IgAN cohort enrolled 20 pts (median age 44.5 y, 50% women, 45% White, 45% Asian); 19 pts completed 52 wks of treatment. BL median 24h total urine protein was 1.2 g/d, 24h UPCR was 0.8 g/g, eGFR was 46 mL/min/1.73m², and systolic/diastolic blood pressure (BP) was 128/82 mmHg.

Reduction in 24h UPCR was evident by Wk 6 (LS mean % change from BL -38.2% [95% CI: -46.6, -28.5]), and sustained through Wk 12 (-48.4% [-56.4, -39.0]) to Wk 52 (-45.4% [-60.7, -24.0]; Fig). Atrasentan was well tolerated with no treatment-related serious adverse events (AEs) or deaths. AEs were seen in 18 pts; one pt discontinued treatment at Wk 13 due to an AE of headache considered treatment related. There was no evidence of significant fluid retention (no clinically meaningful mean changes from BL in body weight, brain natriuretic peptide, or BP).

Conclusion

Atrasentan, in addition to standard of care, was well tolerated and resulted in a clinically meaningful, stable reduction in proteinuria over 1 year of treatment, supporting its therapeutic potential in IgAN. The ongoing global Phase 3 ALIGN study (NCT04573478) is evaluating the effect of atrasentan on proteinuria and kidney function in pts with IgAN.

Funding

• Commercial Support – Chinook Therapeutics Inc, A Novartis Company