Kidney Week

Abstract: FR-OR62

ALIGN Subgroup Analyses: Clinically Meaningful Urinary Protein-to-Creatinine Ratio Reductions across Subgroups

Session Information

• IgA Nephropathy: New Therapies and Insights
  October 25, 2024 | Location: Room 6D, Convention Center
  Abstract Time: 05:30 PM - 05:40 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink, PhD

• Jardine, Meg, University of Sydney, Sydney, New South Wales, Australia

Meg Jardine, MBBS, PhD

• Kohan, Donald E., University of Utah Health, Salt Lake City, Utah, United States

Donald E. Kohan, MD, PhD, FASN

• Lafayette, Richard A., Stanford University, Stanford, California, United States

Richard A. Lafayette, MD

• Levin, Adeera, The University of British Columbia, Vancouver, British Columbia, Canada

Adeera Levin, MD

• Liew, Adrian, Mount Elizabeth Novena Hospital, Singapore, Singapore

Adrian Liew, MD, MBBS, FASN

• Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China

Hong Zhang, MD, PhD

• Gray, Todd E., Chinook Therapeutics, a Novartis Company, Seattle, Washington, United States

Todd E. Gray, MS

• Sheth, Khushboo, Chinook Therapeutics, a Novartis Company, Seattle, Washington, United States

Khushboo Sheth, MD

• Renfurm, Ronny W., Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Ronny W. Renfurm, MD, MBA

• Kocinsky, Hetal S., Chinook Therapeutics, a Novartis Company, Seattle, Washington, United States

Hetal S. Kocinsky, MD

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

Jonathan Barratt, MBChB, PhD

Background

Approximately 30% of IgAN patients (pts) with proteinuria 1–2 g/day develop kidney failure within 10 years; even pts with low levels of persistent proteinuria (<1 g/d) are at risk. Endothelin (ET)-1 upregulation and ET_A receptor activation drive proteinuria, kidney inflammation and fibrosis in IgAN. Atrasentan is a potent and selective ETA receptor antagonist. ALIGN is a Phase 3, randomized, double-blind, placebo-controlled study of the efficacy and safety of atrasentan vs placebo in adult IgAN pts on optimized supportive care (SC).

Methods

Pts with biopsy-proven IgAN and proteinuria of ≥ 1g/day were randomized to receive atrasentan 0.75 mg or placebo orally once daily for 132 weeks while continuing SC. The primary endpoint, the change from baseline (CFB) in proteinuria at Week 36, based on UPCR from 24-hour urine collection was evaluated in a prespecified interim analysis of the first 270/340 patients randomized to the main stratum. Subgroups evaluated included key demographic (gender, age, race, ethnicity and region), and baseline disease characteristics (baseline UPCR, BP, eGFR and diuretic use).

Results

The prespecified interim analysis of the primary endpoint showed a 36.1% (26.4%, 44.6%; p<0.0001) relative reduction in LS mean % UPCR CFB at Week 36. Proteinuria reduction was of similar magnitude regardless of age, sex, race, ethnicity or region, and baseline levels of proteinuria, eGFR, BP or diuretic usage (Fig). Atrasentan was well-tolerated with a favorable safety profile. Results for an exploratory SGLT2i stratum were consistent with the main stratum.

Conclusion

Clinically meaningful proteinuria reductions were observed with atrasentan in all subgroups regardless of baseline demographic or disease characteristics.

Funding

• Commercial Support – Chinook Therapeutics, a Novartis company