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Abstract: FR-OR59

Effect of Iptacopan on Proteinuria and Complement Biomarkers Over Time in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Barratt, Jonathan, University Hospitals of Leicester NHS Trust, Leicester, Leicester, United Kingdom
  • Zhang, Hong, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
  • Rizk, Dana, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Kashihara, Naoki, Kawasaki Ika Daigaku Jinzo Koketsuatsu Naikagaku Kyoshitsu, Kurashiki, Okayama, Japan
  • Maes, Bart D., AZ Delta vzw, Roeselare, West-Vlaanderen, Belgium
  • Trimarchi, Hernan, Hospital Britanico de Buenos Aires, Buenos Aires, Federal District, Argentina
  • Sprangers, Ben, Katholieke Universiteit Leuven Universitaire Ziekenhuizen Leuven Campus Gasthuisberg, Leuven, Flanders, Belgium
  • Meier, Matthias, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland
  • Kollins, Dmitrij, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland
  • Magirr, Annabel Rose, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland
  • Junge, Guido, Novartis Institutes for BioMedical Research Basel Department of Translational Medicine, Basel, Basel-Stadt, Switzerland
  • Perkovic, Vlado, University of New South Wales, Sydney, New South Wales, Australia
Background

The alternative complement pathway (AP) plays a key role in the pathogenesis of IgA nephropathy (IgAN). Iptacopan (LNP023) is an oral, first in class, highly-potent, selective inhibitor of factor B (FB). In a Phase 2 study, iptacopan treatment led to a dose dependent reduction in proteinuria and inhibition of AP in patients with IgAN.

Methods

This parallel-group adaptive design Phase 2 study (NCT03373461) randomized biopsy-confirmed IgAN patients to one of the four iptacopan doses (10, 50, 100, or 200 mg bid) or placebo for either a 3-month (m) (Part 1; N=46) or 6-m (Part 2; N=66) treatment period. In this analysis, we report changes in proteinuria (ratio to baseline in UPCR), and biomarkers of complement activity (plasma Bb, FB, properdin, C3 and C4, and serum Wieslab activity) with iptacopan 200 mg bid (n=26) vs placebo (n=25) at 3 m (pooled part 1 and 2 data) and 6 m (part 2).

Results

UPCR fell by 31% (80% CI: 23%, 39%) and 41% (31%, 49%) from baseline to 3- and 6-m (post-hoc analysis of part 1 and 2) in the iptacopan arm vs 12% (0%, 20%) and 2% (-20%, 23%) in the placebo arm (Figure 1A). Iptacopan selectively inhibited AP as demonstrated by changes in Wieslab activity, Bb, FB, properdin levels (Figure 1B) and small increases in C3; C4 levels remained largely unchanged indicating that iptacopan does not inhibit classical/lectin pathway (Figure 1B).

Conclusion

In accordance with its mechanism of action, iptacopan 200 mg bid attenuates activation of AP and results in clinically meaningful reductions in proteinuria in patients with IgAN.

Effect of iptacopan on proteinuria and complement biomarkers

Funding

  • Commercial Support