140-OR: Durable Glycemic Control and Elimination of Exogenous Insulin Use with VX-880 in Patients with Type 1 Diabetes (T1D)—VX-880-101 (FORWARD)

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. Disclosure M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk. P. Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated. Research Support; Sernova, Corp. Stock/Shareholder; Eledon. T.W. Reichman: Research Support; Vertex Pharmaceuticals Incorporated. Advisory Panel; Novo Nordisk. E.J. de Koning: None. J.F. Markmann: Consultant; iTolerance, Inc, Vertex Pharmaceuticals Incorporated. J.S. Odorico: Other Relationship; Regenerative Medical Solutions, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Other Relationship; Vertex Pharmaceuticals Incorporated, Veloxis. Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; UpToDate, Sernova, Corp. M. Wijkstrom: Consultant; Vertex Pharmaceuticals Incorporated. L.S. Kean: Consultant; Vertex Pharmaceuticals Incorporated. Research Support; Bristol-Myers Squibb Company, Tessera, Gilead Sciences, Inc, Novartis Pharmaceuticals Corporation. Advisory Panel; HiFi Bio. Research Support; Tonix, Merck & Co., Inc. C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc. A.L. Peters: Advisory Panel; Medscape. Consultant; Vertex Pharmaceuticals Incorporated. Research Support; Insulet Corporation, Abbott. Other Relationship; Omada Health. Y. Tan: None. K. Vanijcharoenkarn: None. D. Melton: Employee; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Sana Biotechnology. F. Pagliuca: Employee; Vertex Pharmaceuticals Incorporated. B. Bruinsma: Employee; Vertex Pharmaceuticals Incorporated. G. Marigowda: Employee; Vertex Pharmaceuticals Incorporated. C. Ricordi: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novo Nordisk.