In a groundbreaking development for organ transplantation, Massachusetts General Hospital (MGH) has successfully completed its second pig-to-human kidney xenotransplant using Eledon Pharmaceuticals' investigational anti-CD40L antibody, tegoprubart, as a crucial component of the immunosuppression regimen. The procedure, performed on January 25, 2025, has already shown promising results, with the patient being discharged from the hospital and successfully discontinuing dialysis for the first time in over two years.
Advancing Xenotransplantation Through Novel Immunosuppression
The transplant, conducted in collaboration with eGenesis, builds upon MGH's first successful xenotransplant performed in March 2024. The FDA granted approval for this procedure in December 2024, paving the way for two additional xenotransplants planned for this year.
Dr. David-Alexandre C. Gros, Eledon's Chief Executive Officer, emphasized the significance of CD40 Ligand blockade in xenotransplantation: "Blocking the CD40 Ligand is a critical component of the immunosuppression regimen for effective translation of organ transplant from nonhuman primates into humans. Our anti-CD40L antibody tegoprubart represents a novel approach to immunosuppression therapy with the potential to improve safety and efficacy."
Mechanism and Clinical Progress
Tegoprubart's mechanism of action involves blocking CD40L and inhibiting multiple costimulatory receptors, including CD40 and CD11, which are essential for immune cell communication. The drug has demonstrated a favorable safety and tolerability profile across multiple potential indications, including kidney allotransplantation.
Dr. Leonardo Riella, Medical Director for Kidney Transplantation at MGH, highlighted the critical nature of this advancement: "Immunosuppression presents one of the greatest challenges for transplantation in both human and non-human organs. The need for advancements in immunosuppressive medications is critical for advancing our field and improving the quality of life for transplant patients everywhere."
Broader Applications and Ongoing Research
Tegoprubart's potential extends beyond kidney xenotransplantation. The drug was previously used in the second-ever pig-to-human heart transplant at the University of Maryland Medical Center in September 2023. Currently, it is being evaluated in three global clinical studies for kidney transplant rejection prevention and in a separate trial for islet transplant rejection in type 1 diabetes patients.
Recent data from an investigator-initiated islet transplant trial at the University of Chicago Medicine Transplant Institute showed promising results, potentially marking the first cases of insulin independence achieved using an anti-CD40L monoclonal antibody therapy without tacrolimus, the current standard of care.
Future Milestones
Eledon Pharmaceuticals has outlined several upcoming milestones for tegoprubart's development program:
- Updated interim clinical trial results from ongoing Phase 1b studies expected summer 2025
- Topline results from Phase 2 BESTOW kidney transplant trial in Q4 2025
- Extended follow-up results from the UChicago Medicine islet transplant trial later this year
This successful xenotransplantation represents another crucial step forward in addressing the global organ shortage crisis while potentially establishing a new standard for transplant immunosuppression therapy.
