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Abstract: FR-PO0804

Absolute Proteinuria over Time with Nefecon vs. Placebo in Patients with IgAN: Results from the Phase 3 NefIgArd Trial

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Reich, Heather N., Division of Nephrology, University Health Network, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • Rovin, Brad, Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Lafayette, Richard A., Division of Nephrology, Department of Medicine, Stanford University, Stanford, California, United States
  • Jones, Russell, Calliditas Therapeutics AB, Stockholm, Sweden
  • Barratt, Jonathan, College of Life Sciences, University of Leicester, Leicester, United Kingdom
Background

Proteinuria reduction is a surrogate marker of immunoglobulin A nephropathy (IgAN) treatment effectiveness. Kidney Disease: Improving Global Outcomes (KDIGO) 2021 guidelines consider an absolute reduction to <1 g/day a “reasonable treatment target”. Nefecon is a targeted–release budesonide formulation approved for IgAN. Here, we present absolute proteinuria over time during the Phase 3 NefIgArd trial.

Methods

Patients were randomized 1:1 to 16 mg/day nefecon or placebo for 9 months, followed by 15 months off treatment. Absolute urine protein–creatinine ratio (UPCR) changes from baseline over time were derived using results from the mixed effect model repeated measurement on the log-transformed data at months 3, 6, 9, 12, 18, and 24, per the NefIgArd co-primary analysis of UPCR. The percentage change from baseline was then back-transformed using the baseline geometric mean UPCR per treatment group.

Results

Absolute geometric mean UPCR decreased by 33.6%, from 1.30 g/gram at baseline to 0.86 g/gram at 9 months with nefecon treatment, with continued reduction to 0.63 g/gram at 12 months (Figure). After month 6 and up until month 24, UPCR remained below 1 g/gram. UPCR was 1.26 g/gram with placebo at baseline and remained relatively stable over time (range 1.17–1.25 g/gram). UPCR response of ≤0.5 g/gram was achieved by 34.6% of patients receiving nefecon versus 10.4% receiving placebo.

Conclusion

In the NefIgArd trial, nefecon led to a substantial and sustainable reduction in proteinuria; no appreciable reduction was seen with placebo. Mean proteinuria levels below 1 g/gram were observed with nefecon from 6 months and continued throughout the off-treatment phase to month 24.

Funding

  • Commercial Support – Calliditas Therapeutics

Digital Object Identifier (DOI)