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Abstract: TH-PO497

Atrasentan for the Treatment of IgA Nephropathy: Interim Results From the AFFINITY Study

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Rastogi, Anjay, University of California Los Angeles, Los Angeles, California, United States
  • Rheault, Michelle N., University of Minnesota Division of Pediatric Nephrology, Minneapolis, Minnesota, United States
  • Kim, Sung Gyun, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)
  • Vo, Nam D., Mountain Kidney and Hypertension Associates, Asheville, North Carolina, United States
  • Ranganathan, Dwarakanathan, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
  • Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
  • Packham, David K., Melbourne Renal Research Group, Reservoir, Victoria, Australia
  • Vishnepolsky, Mark, Kidney Specialists of Southern Nevada, Las Vegas, Nevada, United States
  • Sheth, Khushboo, Chinook Therapeutics Inc, Seattle, Washington, United States
  • DeVries, Todd, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Camargo, Marianne, Chinook Therapeutics Inc, Seattle, Washington, United States
  • King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States
  • Jones-Burton, Charlotte, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Wong, Muh Geot, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
Background

Endothelin A (ETA) receptor activation drives proteinuria, inflammation, and fibrosis in patients with glomerular diseases. Atrasentan, a potent and selective ETA receptor antagonist, represents a potential therapy to reduce proteinuria and preserve kidney function in patients with IgA nephropathy (IgAN) and other glomerular diseases. AFFINITY is a global, phase 2, open-label basket study to evaluate the efficacy and safety of atrasentan in adult patients with IgAN, Alport syndrome, FSGS & DKD. Here we present interim results of the IgAN cohort through week 24 of treatment.

Methods

Eligibility criteria for the IgAN cohort include adults with biopsy-proven IgAN; eGFR ≥30 mL/min/1.73 m2, UPCR ≥0.5 g/g and <1.0 g/g (first morning void) and on max tolerated/stable RASi. Patients are treated orally with 0.75 mg atrasentan daily for 52 weeks. The primary endpoint is change in 24-hour UPCR from baseline to Week 12.

Results

Twenty patients have enrolled in the IgAN cohort. Median age was 45 years, with 50% women, 45% White and 45% Asian. Baseline 24-hour total urine protein was 1.1 g/day (geometric mean; GM), 70% of subjects having total urine protein of >1 g/day, and median eGFR is 46 mL/min/1.73m2. GM percent reduction from baseline in 24-hour UPCR was 49.9% at week 12 (95% CI 39.8 ,58.3; n=18) and 58.6% at week 24 (95% CI 50.5, 65.5; n=13; Figure). There were no treatment-related severe adverse events (AEs). Treatment-emergent AEs observed in 16 patients were mild or moderate in severity, and most have resolved. One patient discontinued treatment due to a related AE of headache at week 13.

Conclusion

Treatment with atrasentan in addition to standard of care was generally well-tolerated and resulted in a clinically meaningful reduction in proteinuria at weeks 12 and 24, strongly supporting the therapeutic potential of ETA receptor blockade with atrasentan in patients with IgAN.

Funding

  • Commercial Support