Eledon Pharmaceuticals announced positive initial data from an investigator-initiated trial at the University of Chicago Medicine, where tegoprubart, an investigational anti-CD40L antibody, was used as part of an immunosuppression regimen following islet transplantation in subjects with type 1 diabetes (T1D). The trial demonstrated the potential for insulin independence without tacrolimus, the current standard of care.
Insulin Independence Achieved
Two out of the first three subjects treated with tegoprubart achieved insulin independence and maintained normal blood glucose control. The third subject, recently transplanted, is on track for insulin independence, showing a significant reduction in insulin use.
Enhanced Islet Engraftment
Islet engraftment in the first two subjects treated with tegoprubart was estimated to be three to five times higher than in comparable subjects receiving tacrolimus-based immunosuppression. This suggests that tegoprubart may be less toxic to transplanted islets, leading to improved graft survival and function.
Safety and Tolerability
Tegoprubart treatment was generally well tolerated in all subjects, with no unexpected adverse events or severe hypoglycemic episodes reported.
Clinical Data
The first participant, a 42-year-old female, experienced an improvement in HbA1c levels from 8.4% to 6.0% at 90 days post-transplant, with a reduction in daily insulin dose from 80 units to 16 units. After a second islet transplant at 16 weeks, she achieved insulin independence and maintained HbA1c levels of 5.4%.
The second participant, a 30-year-old female, discontinued insulin support four weeks after the islet transplant. Her HbA1c levels improved from 8.5% to below 5.8% starting at seven weeks post-transplant.
The third participant, a 37-year-old male, was discharged home on day three post-transplant, requiring 29 units of insulin, reduced from 90 units per day at baseline. His baseline HbA1C was 9.3%.
Expert Commentary
"These data are another step in our quest to achieve a path for functional cures in type 1 diabetes," said Piotr Witkowski, M.D., Ph.D., Director, Pancreas and Islet Transplant Program, UChicago Medicine. He added that tegoprubart could be a novel immunosuppression option, advancing islet transplantation as a potentially transformational alternative for subjects with type 1 diabetes.
About Tegoprubart
Tegoprubart is an investigational anti-CD40L antibody being developed by Eledon Pharmaceuticals. It is designed to modulate the immune system and prevent transplant rejection. The trial is also supported by grants from Breakthrough T1D and The Cure Alliance.
About Islet Transplantation
Islet transplantation is a minimally invasive procedure aimed at providing blood glucose control for subjects with type 1 diabetes, reducing or eliminating their dependence on insulin. The procedure involves infusing pancreatic islets from a deceased donor into the patient's liver, where they release insulin. Immunosuppression therapy is required post-procedure to prevent transplant rejection.
