Abstract
Introduction and Objective: VX-880 is an allogeneic stem cell-derived, fully differentiated islet cell therapy in clinical development for T1D.
Methods: This single-arm, open-label, phase 1/2/3 trial is evaluating VX-880 in T1D adults with impaired hypoglycemia awareness and ≥2 severe hypoglycemic episodes (SHEs) the year before enrollment. Participants receive a standard immunosuppression regimen. Enrollment and dosing in the phase 1/2 portion has completed and phase 3 is ongoing.
Results: These results reflect 12 participants who received a full VX-880 dose as a single infusion and were followed for at least one year, as of October 2024. At baseline, all participants had multiple SHEs and undetectable fasting C-peptide. All 12 participants demonstrated engraftment with glucose responsive C-peptide production at Day (D)90 MMTT which was durable through Month (M)12. All 12 participants achieved ADA HbA1c target of <7% (mean: baseline=7.8%; M12=6.0%) and time in range target of >70% (mean: baseline=49.5%; M12=93%); and all were free of SHEs from D90 onwards. All 12 participants had reduction in exogenous insulin use (mean reduction: 92%) and 10/12 (83%) no longer required exogenous insulin at M12. Median duration free of exogenous insulin was 232 (69 to 441) days. All 12 participants were evaluable for and achieved the phase 1/2 primary endpoint of elimination of SHEs and HbA1c <7%. Most adverse events (AEs) were mild or moderate in severity. There were no VX-880-related serious AEs. Two deaths occurred; both were reported previously and unrelated to VX-880. Overall, the safety profile was consistent with the immunosuppressive regimen and islet infusion procedure.
Conclusion: These durable clinical benefits of VX-880 with elimination of SHEs, improved glycemic control, and freedom from exogenous insulin support the curative potential of VX-880, the first and only allogeneic, stem-cell derived, islet cell therapy in pivotal development.