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Abstract: SA-PO887

Atacicept 150 mg Reduces Serum Gd-IgA1, a Biomarker Associated with Long-Term Outcomes in IgA Nephropathy (IgAN): 36W Results from the Ph2b ORIGIN Study

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
  • Maes, Bart D., AZ Delta vzw, Roeselare, West-Vlaanderen, Belgium
  • Lin, Celia J.F., Vera Therapeutics, Inc., Brisbane, California, United States
  • Wei, Xuelian, Vera Therapeutics, Inc., Brisbane, California, United States
  • Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
  • Phoon, Richard K S, The University of Sydney, Sydney, New South Wales, Australia
  • Kim, Sung Gyun, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea (the Republic of)
  • Tesar, Vladimir, Univerzita Karlova, Praha, Czechia
  • Floege, Jürgen, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Nordrhein-Westfalen, Germany
  • Jha, Vivekanand, The George Institute for Global Health India, New Delhi, Delhi, India
  • Lafayette, Richard A., Stanford University, Stanford, California, United States
Background

IgA nephropathy (IgAN), the most common primary glomerulonephritis and a significant contributor to ESRD worldwide, is characterized by elevated serum levels of galactose-deficient immunoglobulin A1 (Gd-IgA1). High Gd-IgA1 levels are associated with greater risk of renal function deterioration. Gd-IgA1 production is driven by the B Lymphocyte Stimulator (BLyS)–A PRoliferation-Inducing Ligand (APRIL) signaling pathway’s effect on B cells and plasma cells. Atacicept is a dual anti-BLyS/APRIL fusion protein in clinical development for IgAN treatment. The Ph2b ORIGIN study of atacicept in IgAN met its primary endpoint. The objective of this analysis is to evaluate change in serum Gd-IgA1 quartiles over 36 weeks (w) with atacicept 150mg, the dose being evaluated in a pivotal Ph3 study, vs placebo (PBO).

Methods

The randomized, double-blind, PBO controlled Ph2b ORIGIN study included 116 patients (pts) with biopsy-proven IgAN, eGFR ≥30mL/min/1.73m2, and urine protein >0.75g/24h or UPCR >0.75g/g despite optimized renin–angiotensin system blockade. Pts were randomized 2:2:1:2 to atacicept 150, 75, or 25 mg vs PBO SC qw for 36w. At baseline (BL), 4, 12, 24, and 36w, Gd-IgA1 values were assessed and classified into quartiles using cutoffs derived from BL Gd-IgA1 values.

Results

Atacicept 150mg (n=30) achieved 64% mean Gd-IgA1 reduction vs 7% for PBO (n=29) at 36w (p<0.001) in pts with BL and 36w data. Atacicept 150mg led to steady Gd-IgA1 reduction to the lowest quartile 1 at 36w in 27/33 pts while most PBO pts transiently increased or decreased by 1 quartile (Figure). In the atacicept 150mg arm, 5/8 pts with BL quartile 4 had reductions to quartile 1 at 36w, while in the PBO arm 8/9 with BL quartile 4 remained in quartile 3 or 4 at 36w.

Conclusion

Atacicept 150mg achieved a durable and significant Gd-IgA1 reduction over 36w. Regardless of BL quartile, the vast majority of pts receiving atacicept 150mg for 36w had Gd-IgA1 reductions to the lowest quartiles, which has been associated with greater renal survival. These results provide further evidence supporting atacicept as a potential disease-modifying treatment for IgAN.

Funding

  • Commercial Support – Vera Therapeutics, Inc.