Tegoprubart delivers insulin independence in islet cell transplant trial

Trial data presented at the American Diabetes Association’s 86^th Scientific Sessions highlight the promise of tegoprubart as an immunosuppressive treatment for people with type 1 diabetes receiving pancreatic islet cell transplants. In the pilot study, all 12 participants became insulin independent, with improved transplanted islet survival and no reported episodes of rejection.

Pancreatic islet transplantation is a minimally invasive procedure developed to provide blood glucose control for people with type 1 diabetes and reduce, or eliminate, dependence on insulin. Islets, which contain insulin-secreting beta-cells, are isolated from the pancreas of a deceased donor and infused into the recipient’s liver via the portal vein. Once established, they begin to release insulin.

For those receiving donor cells, daily immunosuppressant medication is needed to prevent transplant rejection. However, these drugs, including the commonly used calcineurin inhibitors (CNIs), can damage insulin-producing cells and are associated with kidney toxicity, hypertension and neurological side effects.

As part of a CNI-free pilot study, the Eledon investigators evaluated tegoprubart, a humanised monoclonal antibody, for its potential to protect islet grafts while avoiding CNI-related toxicity. The study enrolled 12 adults with long-standing type 1 diabetes and repeated hypoglycaemic events (median diabetes duration, 33 years; mean HbA_1c, 8.0% [64 mmol/mol]).

Following islet transplantation and treatment with tegoprubart, all showed rapid improvement in glycaemic control. Across the cohort, no rejection episodes or signals of graft failure were observed over a median post-transplant follow-up of 8 months and a maximum follow-up of 22 months.

All 12 participants achieved insulin independence, producing their own insulin and no longer requiring exogenous insulin therapy. Each had a most recent HbA_1c measurement below the clinical threshold for diabetes of 6.5% (48 mmol/mol), with a cohort mean of 5.4% (36 mmol/mol). No severe hypoglycaemic episodes were reported.

Compared with historical patients treated with CNIs at the same centre, three and five times more transplanted islet cells survived. Tegoprubart was generally well tolerated, with no evidence of the toxic side effects associated with CNIs.

The investigators suggest that the emerging promise of tegoprubart may signal a future in which islet-cell grafts are protected without the burden of traditional immunosuppression. Further research is planned to evaluate tegoprubart in individuals with type 1 diabetes and chronic kidney disease.