Two out of three patients with type 1 diabetes achieved insulin independence following islet transplantation using an immunosuppression regimen that included tegoprubart, according to initial data from an investigator-initiated trial at the University of Chicago Medicine's Transplantation Institute. The study evaluated tegoprubart, Eledon Pharmaceuticals’ anti-CD40L antibody, as part of the immunosuppressive therapy.
Type 1 diabetes, an autoimmune disease affecting approximately 2 million Americans, or 5% to 10% of all diabetes cases, often necessitates lifelong insulin therapy. Pancreatic islet transplantation offers a potential alternative for blood glucose control by replacing damaged insulin-producing beta cells. However, post-transplant immunosuppression is crucial to prevent rejection of the transplanted islets.
The study results, presented at the International Pancreas and Islet Transplantation Association (IPITA), Harvard Stem Cell Institute (HSCI), and Breakthrough T1D Summit on Stem Cell Derived Islets on October 29, 2024, indicate that tegoprubart may offer a less toxic immunosuppression approach. Islet engraftment in the first two patients was estimated to be three to five times higher than in comparable patients receiving the current standard of care tacrolimus-based immunosuppression, suggesting improved graft survival and function.
Study Details and Outcomes
Patients in the study received islet transplants combined with induction therapy, mycophenolate mofetil, and tegoprubart, administered intravenously every three weeks. The first two patients achieved insulin independence approximately 2 to 6 months post-transplant, maintaining normal HbA1c levels. The third patient experienced a reduction in insulin use by more than 60% within the first few days after transplantation.
According to Piotr Witkowski, M.D., Ph.D., director of the Pancreas and Islet Transplant Program at the University of Chicago Medicine, the data represent "an important step toward achieving functional cures for type 1 diabetes through improved immunosuppression approaches that minimize side effects."
Safety and Tolerability
The treatment with tegoprubart was generally well-tolerated, with no unexpected adverse events or severe hypoglycemic episodes reported during the study. This favorable safety profile is particularly important, as conventional immunosuppressants can have significant side effects, including toxicity to the kidneys, central nervous system, and islet cells, as well as increased risk of diabetes and hypertension.
Future Directions
Tegoprubart is also being investigated in a phase 2 trial sponsored by Eledon Pharmaceuticals for the prevention of organ rejection in kidney transplant patients. This trial has enrolled 120 patients to compare tegoprubart with tacrolimus. Funding for the University of Chicago study was provided by grants from Breakthrough T1D (formerly JDRF) and The Cure Alliance.
