ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2022 and some content may be unavailable. To unlock all content for 2022, please visit the archives.

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 –