In an investigator-initiated islet transplant study in type 1 diabetes, 6 of 6 patients achieved insulin independence on a tacrolimus-free regimen built around tegoprubart, an anti-CD40L antibody. HbA1c was maintained below 6% in recent recipients and as low as 4.7% in one patient out to 15 months. No severe hypoglycemia, serious infections, thromboembolic events, rejection episodes, or calcineurin inhibitor–associated kidney or neurologic toxicities were reported.
Eledon Pharmaceuticals reported preliminary results from the first six subjects in a University of Chicago Medicine trial evaluating tegoprubart as the backbone of calcineurin inhibitor–free immunosuppression to prevent islet graft rejection in type 1 diabetes. The ongoing study has been extended to 12 subjects. Most patients reached insulin independence after a single islet infusion within about four weeks; one required a second infusion. Data were presented at the Rachmiel Levine–Arthur Riggs Diabetes Research Symposium, and Breakthrough T1D is funding the trial and a planned follow-on study in patients with chronic kidney disease.
Strategically, these data target the central liability of islet transplantation: durable glycemic benefit constrained by immunosuppression toxicity. Standard tacrolimus-based regimens carry nephrotoxicity, neurotoxicity, and metabolic side effects that limit eligibility and long-term use. By positioning tegoprubart as a non–calcineurin backbone, Eledon is aiming to redefine the risk–benefit threshold in a niche that gained regulatory momentum with FDA’s approval of an allogeneic islet product but still lacks a tolerable, scalable immunosuppression paradigm. The early safety signal also addresses a long-standing class concern with anti-CD40L agents—thromboembolic risk—by showing a clean profile in the first six subjects, though numbers remain small.
For sites, a tacrolimus-free protocol could expand candidates, simplify post-transplant metabolic management, and reduce renal monitoring burdens, particularly relevant as programs consider patients with pre-existing kidney impairment. However, an antibody-based regimen introduces infusion logistics, capacity planning, and vigilance for immunogenicity and infection risk as exposure lengthens. Sponsors and CROs in diabetes cell therapy should view this as potentially enabling infrastructure: if a safer co-therapy can reliably protect grafts, it lowers the operational hurdle for emerging sources of beta cells, including iPSC-derived islets and xenogeneic platforms—areas Eledon is also pursuing. Regulators will look for standardized endpoints beyond insulin independence and HbA1c, including C-peptide AUC, time-in-range, graft survival, donor-specific antibodies, and infection profiles, with durability past 12–24 months central to any registrational path.
The practical constraint remains supply and standardization of islet material, which can confound cross-study comparisons and scalability. If tegoprubart’s effect is robust across variable islet quality and dosing, it strengthens the case for a drug-centric approval strategy; otherwise, tighter pairing with a defined cell product may be necessary. The current dataset is small, uncontrolled, and investigator-led, so the next inflection points are enrollment of the expanded 12-subject cohort, longer follow-up on the earliest recipients, and clarity on company-sponsored, controlled trials that benchmark against tacrolimus-based standards. Watch for signals on thrombosis and serious infections as N and exposure increase, dosing cadence and infusion resource requirements at scale, and whether the CKD cohort can maintain renal stability without CNI exposure.
If durability and safety hold, tegoprubart could shift islet transplantation from a last-resort option to a more broadly considered intervention—and potentially inform tac-free strategies in kidney and xenotransplantation. The risk is that small-sample enthusiasm gives way to class-typical complications or incremental benefit once tested against optimized CNI regimens. The read-through for the field is clear: immunoprotection that reduces systemic toxicity is becoming the gating factor for beta cell replacement technologies, and the winners will be those who can pair consistent graft performance with operationally manageable immune modulation.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
