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Kidney Week

Abstract: FR-OR56

NeflgArd Open-Label Extension: Efficacy and Safety of Nefecon in Patients with IgAN Who Completed the 2-Year Phase 3 Trial

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Lafayette, Richard A., Division of Nephrology, Department of Medicine, Stanford University, Stanford, California, United States
  • Kristensen, Jens, JDK Pharmaconsulting, Espergarde, Denmark
  • Jones, Russell, Calliditas Therapeutics AB, Stockholm, Stockholm County, Sweden
  • Floege, Jürgen, Department of Nephrology and Clinical Immunology, Rheinisch Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
  • Tesar, Vladimir, Department of Nephrology, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czechia
  • Trimarchi, Hernan, Nephrology Service, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
  • Reich, Heather N., Division of Nephrology, University Health Network, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • Zhang, Hong, Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China
  • Rovin, Brad H., Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Barratt, Jonathan, College of Medicine Biological Sciences and Psychology, University of Leicester, Leicester, United Kingdom
Background

Nefecon was approved for the reduction of kidney function loss in adults with primary immunoglobulin A nephropathy (IgAN) at risk of disease progression, based on the 2-year NeflgArd trial findings (Lafayette. Lancet 2023;402:859). Nefecon 16 mg/d for 9 months (mo.) led to a statistically significant benefit in time-weighted average estimated glomerular filtration rate (eGFR) and a durable proteinuria reduction vs placebo. We report data from an open-label extension (OLE) study (NCT04541043) of the effect of Nefecon treatment (tx) in patients (pts) who completed the NeflgArd trial.

Methods

This Phase 3b, multicenter, OLE enrolled pts with IgAN who completed the NeflgArd trial, with persistent proteinuria ≥1 g/d or urine protein–creatinine ratio (UPCR) ≥0.8 g/g and eGFR ≥30 mL/min/1.73 m2 despite optimized renin–angiotensin system blockade. Pts who completed a full 9-mo. course of Nefecon 16 mg/d without dose reductions were included. OLE pts received Nefecon 16 mg/d for 9 mo. (+2 wks’ tapering at 8 mg/d). Blinding to previous NefIgArd tx was maintained. Primary efficacy endpoints were the ratios of eGFR and UPCR at 9 mo. vs OLE baseline. Adverse events occurring during the OLE were captured as new or ongoing from the NefIgArd trial.

Results

Of the 326 pts completing the NefIgArd trial, 119 entered the OLE (45 [38%] Nefecon-experienced; 74 [62%] Nefecon-naïve). 94 (79%) pts were men and 100 (84%) identified as white. At the OLE baseline, median eGFR in Nefecon-experienced vs Nefecon-naïve pts was 50.4 and 49.2 mL/min/1.73 m2, respectively; median UPCR was 1.28 and 1.37 g/g, respectively. For all 119 pts, UPCR reduction from baseline at 9 mo. was 32%, with an absolute eGFR decline of 1.43 mL/min/1.73 m2 also reported. In the OLE, similar UPCR reductions and eGFR changes after 9 mo. of Nefecon were seen in Nefecon-experienced and -naïve pts. Tx in the OLE was well tolerated without any new safety signals.

Conclusion

These study findings provide valuable insights into the efficacy and safety of additional tx with Nefecon and demonstrate that, in pts previously treated with Nefecon, a second 9-mo tx course had an effect on proteinuria and kidney function decline similar to a first tx course, without additional safety concerns.

Funding

  • Commercial Support – Calliditas Therapeutics AB