TRANSFORMATIVE PRE-CLINICAL STUDY LED BY DIABETES RESEARCH INSTITUTE ENABLES FIRST SUCCESSFUL CLINICAL TRIAL WITH ANTI-CD40L ANTIBODY
MIAMI (October 29, 2024) – In a major advancement for type 1 diabetes (T1D) treatment, the University of Miami Diabetes Research Institute (UM-DRI), in collaboration with the University of Chicago, is pioneering the use of Tegoprubart (Eledon Pharmaceuticals, Irvine, CA), a novel anti-CD40L antibody, as an alternative to Tacrolimus in islet transplantation. UM-DRI’s extensive preclinical research laid the foundation for the FDA-approved human trial which is now underway at the University of Chicago.
Research and subsequent clinical trial results were presented today at the 5th Annual Summit on Stem Cell Derived Islets in Boston, MA.
Pre-clinical research at UM-DRI, supported in part by the Diabetes Research Institute Foundation (DRIF), was led by Dr. Norma Kenyon (Deputy Director and Professor of Surgery, Microbiology, Immunology and Biomedical Engineering at the UM-DRI) and Dr. Camillo Ricordi (Director of the Cell Transplant Center and Director Emeritus of the DRI, Professor and Chief of the Division of Cellular Transplantation). Their work demonstrated the safety and efficacy of Tegoprubart in large pre-clinical models, paving the way for the FDA-approved clinical trial at the University of Chicago, led by Dr. Piotr Witkowski (Professor of Surgery and Director of the Pancreatic and Islet Transplant Program at the University of Chicago).
New Approach, Reduced Toxicity
For patients in the clinical trial, donor pancreatic islets (the mini-organs containing insulin-producing cells) were infused into the liver by a minimally invasive procedure through a catheter placed by the interventional radiologist under local anesthesia. Traditionally, patients undergoing islet transplantation have relied on Tacrolimus, a calcineurin inhibitor with notable side effects. However, this new approach with Tegoprubart has the potential to minimize toxicity while preserving transplanted islet function. This advancement marks a substantial shift, as CD40L antibodies, unlike Tacrolimus, aim to condition the immune system to accept transplanted cells as “self,” thereby lowering the risk of immune rejection and potentially improving insulin production and stability. In pre-clinical trials at UM-DRI, this approach enabled higher rates of insulin secretion post-transplant, with no observed sign of toxicity toward the transplanted islets, kidneys, or other organs.
All trial patients received this novel therapy at the University of Chicago. Two female patients with T1D, age 40 and 30, showed excellent control of glucose levels without the need for insulin injections, after decades of inability to control their blood sugar and living in constant danger of debilitating, potentially lethal episodes of low blood sugar (hypoglycemia). A third patient with T1D had already received the anti-CD40L therapy with remarkable results that were also presented at the Boston meeting.
“There is clinical evidence from our studies and others conducted by the NIH’s Clinical Islet Transplantation Consortium that demonstrate islet transplantation can reverse diabetes,” said Dr. Witkowski. “However, the use of current standard of care anti-rejection medications, specifically calcineurin inhibitors like Tacrolimus, have limited the benefit of these procedures due to well-known associated toxicity to the islets and the kidneys, in addition to neurotoxicity and an increased risk of hypertension. Our initial results indicate that Tegoprubart can effectively protect islets from rejection without the side effects related to current standard therapy.”
Supported by The Cure Alliance (TCA), Breakthrough T1D and the DRIF, this pilot trial highlights decades of dedication by UM-DRI scientists, notably Drs. Kenyon and Ricordi, who have consistently advanced the field of islet transplantation. With longstanding support from the DRIF, UM-DRI remains at the forefront of finding safer, more effective diabetes therapies. This novel antibody approach, developed with Eledon Pharmaceuticals, holds potential for true insulin independence.
“It has been a long journey to help people with type 1 diabetes become free from dependence on insulin,” said Dr. Ricordi. “This strategy holds great promise!”
About the Diabetes Research Institute Foundation (DRIF)
The Diabetes Research Institute Foundation (DRIF), a 501(c)(3) not-for-profit corporation, is the organization of choice for those who are serious, passionate and committed to preventing and curing diabetes. Our mission – to provide the Diabetes Research Institute with the funding necessary to advance critical research – is a testament to the belief that tomorrow is not soon enough to change the lives of people living with diabetes.
The Diabetes Research Institute (DRI) is a comprehensive, multidisciplinary research center and recognized world leader in the field. By working in close collaboration with cure-focused partners in real-time across the globe, we can accelerate the pace of discovery and ensure that the best ideas are quickly translated into actionable clinical research.
DRI Foundation donors support researchers with funding necessary to initiate critical cure-focused research, thus better positioning our scientists to compete for additional research funding. Donor support is also an important source of bridge funding, which researchers utilize to cover funding gaps and to accelerate the translation of novel research into transformational therapies for patients. Private philanthropic support is the backbone of the DRI’s ability to innovate. For more information, please visit DiabetesResearch.org or call 800-321-3437.
Media Contacts:
Michael Myers, Chief Communications Officer
Diabetes Research Institute Foundation
(847) 208-6920 or mmyers@drif.org
Christina Khoury-Folkens, Media Lead
Real Chemistry
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