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Kidney Week

Abstract: FR-PO1118

Anti-CD40 (Iscalimab) Treatment Results in Preserved Allograft Histology in Non-Human Kidney Transplantation Compared with Calcineurin Inhibitors

Session Information

  • Transplantation: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Rush, James, Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Wieczorek, Grazyna, Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Mihatsch, Michael J., University Hospital Basel, Basel, Switzerland
  • Ceci, Melanie, Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Naumann, Ulrike, Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Ferrero, Enrico, Novartis Institutes for Biomedical Research, Basel, Switzerland
  • Haraldsson, Boerje, Novartis Pharma AG, Basel, Switzerland
Background

The CD40-CD154 costimulatory pathway has been implicated in the pathology of transplant rejection, and blockade of this interaction using anti-CD40 antibodies significantly prolongs renal allograft survival in non-human primates (NHPs). Further, recent clinical data indicated that the anti-CD40 mAb Iscalimab (CFZ533) demonstrated comparable efficacy and superior renal function versus tacrolimus in de novo calcineruin inhibitor (CNI)-free kidney transplantation. One possible explanation for superior renal function was that Iscalimab treatment may have resulted in improved graft quality compared to CNIs, a notion supported by data from a small number of patients from the aforementioned clinical study.

Methods

To further examine this notion, allograft histology from baseline and up to one hundred days post-transplanted NHP kidney allografts from transplanted animals treated with Iscalimab, anti-CD154 mAb, Cyclosporine A, PKC inhibitors or FTY720 were reviewed and scored in a blinded fashion by a pathologist according to the Banff classification.

Results

In addition, we performed molecular analyses of these samples. Our analyses indicated that the quality of allografts as defined using total, inflammatory and fibrotic BANFF scores, from Iscalimab treated animals were superior to that observed in animals dosed with all other immunomodulatory and immunosuppressive agents. This was also reflected in the molecular analyses of allograft biopsies showing that CFZ533 was more likely to preserve the gene expression profile of baseline tissue following transplantation compared to other drugs.

Conclusion

Collectively our data indicated that prevention of allograft rejection by Iscalimab appears to be associated with higher graft quality compared to other drugs, including CNIs.

Funding

  • Commercial Support