Atrasentan in Patients with IgA Nephropathy

Area of Science:

• Nephrology
• Clinical Pharmacology
• Immunology

Background:

• IgA nephropathy (IgAN) patients with severe proteinuria face a high risk of kidney failure.
• The effectiveness and safety of atrasentan, an endothelin type A receptor antagonist, for reducing proteinuria in IgAN are not fully established.

Purpose of the Study:

• To evaluate the efficacy and safety of atrasentan in reducing proteinuria in adults with biopsy-proven IgA nephropathy.
• To assess the change in 24-hour urinary protein-to-creatinine ratio from baseline to week 36 in patients treated with atrasentan compared to placebo.

Main Methods:

• Phase 3, multinational, double-blind, randomized, controlled trial.
• Adults with IgAN, proteinuria ≥1 g/day, and eGFR ≥30 ml/min/1.73 m² received atrasentan (0.75 mg/day) or placebo for 132 weeks.
• Primary outcome: change in 24-hour urinary protein-to-creatinine ratio at week 36, analyzed via interim analysis of 270 patients.

Main Results:

• Atrasentan demonstrated a significantly greater reduction in proteinuria compared to placebo (-38.1% vs. -3.1%, P<0.001).
• The percentage of patients experiencing adverse events was similar between groups.
• Fluid retention was slightly higher in the atrasentan group (11.2%) but did not lead to trial discontinuation; no cardiac failure or severe edema occurred.

Conclusions:

• Atrasentan provides a significant and clinically meaningful reduction in proteinuria in IgA nephropathy patients.
• This interim analysis supports atrasentan as a potential therapeutic option for managing proteinuria in IgAN.
• The study was funded by Novartis and is registered under ClinicalTrials.gov number NCT04573478.