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 in islet transplantation for subjects with type 1 diabetes (T1D). The results indicate the potential for insulin independence without the use of tacrolimus, the current standard of care.
Key Findings
The study, led by researchers at UChicago Medicine's Transplantation Institute, demonstrated that the first two out of three subjects treated with tegoprubart achieved insulin independence and maintained normal hemoglobin A1C (HbA1c) levels post-transplant. The third subject, who recently underwent the procedure, is showing a positive trajectory toward insulin independence, with a significant reduction in insulin use.
Enhanced Islet Engraftment
Notably, islet engraftment in the first two subjects treated with tegoprubart was estimated to be three to five times higher than that observed 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
The treatment was generally well-tolerated among all subjects, with no unexpected adverse events or hypoglycemic episodes reported during the study period.
Expert Commentary
"We are very pleased that tegoprubart played a pivotal role in yet another landmark advance in transplantation research through the work of Dr. Witkowski, Dr. Fung and their team at UChicago Medicine," said David-Alexandre C. Gros, M.D., Chief Executive Officer of Eledon. "Following promising results in kidney allotransplant procedures as well as heart and kidney xenograft procedures, these data from subjects following islet transplantation further demonstrate tegoprubart’s potential to protect transplanted organs and cells."
Piotr Witkowski, M.D., Ph.D., Director, Pancreas and Islet Transplant Program, UChicago Medicine, added, "These data are another step in our quest to achieve a path for functional cures in type 1 diabetes. For more than 30 years, we have been looking for options that can deliver target levels of immunosuppression without the side effects associated with standard of care, including toxicity to the kidneys, central nervous system and islet cells, and increased risk of diabetes and hypertension."
Study Details
The trial involved islet transplants combined with induction therapy, mycophenolate mofetil (MMF), and tegoprubart, administered intravenously every third week. The first two subjects achieved insulin independence with stable islet graft function at approximately three and six months post-transplant, respectively. One participant, a 42-year-old female, improved her HbA1c level to 6.0% (from 8.4% at baseline) and reduced her daily insulin dose to 16 units per day (from 80 units per day at baseline) at 90 days post-transplant. After a second islet transplant at 16 weeks, she achieved insulin independence, maintaining improved HbA1c levels of 5.4%.
The second participant, a 30-year-old female, ceased insulin support (from 60 units per day at baseline) four weeks after the islet transplant, with HbA1c levels improving to 5.8% and below (from 8.5% at baseline) starting at seven weeks post-transplant.
Future Implications
The data, presented at the International Pancreas and Islet Transplantation Association (IPITA), Harvard Stem Cell Institute (HSCI), and Breakthrough T1D 5th Annual Summit on Stem Cell Derived Islets, suggest that tegoprubart could offer a safer and more effective immunosuppression option for islet transplantation in T1D patients.
