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 the use of tacrolimus, the current standard of care.
Insulin Independence Achieved
In the study, 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 islet transplantation, experienced a reduction in insulin use by more than 60% within three days following the procedure and is on track toward insulin independence.
Enhanced Islet Engraftment
Islet engraftment in the first two subjects treated with tegoprubart was estimated to be three to five times higher than that observed in three comparable subjects who received 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 with tegoprubart was generally well-tolerated among all subjects, with no unexpected adverse events or hypoglycemic episodes reported.
Study Details
The study involved islet transplants combined with induction therapy, mycophenolate mofetil (MMF), and tegoprubart, administered intravenously every third week. The first two subjects achieved insulin independence and demonstrated stable islet graft function at approximately three and six months post-transplant, respectively.
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. Dr. Witkowski's study also further reinforces prior study results showing that tegoprubart may offer a favorable safety and efficacy profile compared to tacrolimus-based immunosuppression regimens."
Implications for Type 1 Diabetes Treatment
"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 and one of the study's lead investigators. "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. These data further support tegoprubart as a novel immunosuppression option that can play a central role in advancing islets transplantation as a potentially transformational alternative for subjects with type 1 diabetes."
Study Participant Outcomes
One participant, a 42-year-old female, saw her HbA1c level improve to 6.0% (from 8.4% at baseline) and her daily insulin dose decrease 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 and maintained improved HbA1c levels of 5.4%.
Another participant, a 30-year-old female, stopped insulin support (from 60 units per day at baseline) four weeks after the islet transplant. Her HbA1c levels improved to 5.8% and below (from 8.5% at baseline) starting at seven weeks after the transplant.
The third participant, a 37-year-old male, was discharged home on day three post-transplant, requiring 29 units of insulin (from 90 units per day at baseline).
Funding and Collaboration
Funding for the study includes grants from Breakthrough T1D (formerly known as JDRF) and The Cure Alliance. Eledon Pharmaceuticals supplied tegoprubart for this investigator-led clinical trial.
