Glucose-Dependent Insulin Production and Insulin-Independence in Type 1 Diabetes from Stem Cell-Derived, Fully Differentiated Islet Cells: Updated Data from the VX-880 Clinical Study
Piotr Witkowski1, Trevor W. Reichman2, Camillo Ricordi3, Ali Naji4, James F. Markmann5, Bruce A. Perkins6, Martin Wijkstrom7, Steven Paraskevas8, Bote G. Bruinsma9, Gautham Marigowda9, Janet Hong9, Chenkun Wang9, Douglas Melton9, Felicia Pagliuca9, Bastiano Sanna9, Leslie S. Kean10, Chantal Mathieu11, Anne Peters12, Michael R. Rickels4.
1Department of Surgery, University of Chicago, Chicago, IL, United States; 2 , Toronto General Hospital, Toronto, ON, Canada; 3 , University of Miami, Miami, FL, United States; 4 , University of Pennsylvania Perlman School of Medicine, Philadelphia, PA, United States; 5 , Massachusetts General Hospital, Boston, MA, United States; 6 , Mount Sinai Hospital, Toronto, ON, Canada; 7 , University of Pittsburgh Medical Center, Pittsburgh, PA, United States; 8 , McGill University Health Centre, Montreal, QC, Canada; 9 , Vertex Pharmaceuticals Incorporated, Boston, MA, United States; 10 , Boston Children’s Hospital and Dana-Farber Cancer Institute, Boston, MA, United States; 11 , Katholieke Universiteit Leuven, Leuven, Belgium; 12 , University of Southern California, Los Angeles, CA, United States
Background and Aims: VX-880 is an allogeneic stem cell-derived, fully differentiated, pancreatic islet cell replacement therapy being evaluated in a Phase 1/2 clinical trial in patients with T1D and impaired awareness of hypoglycemia and severe hypoglycemia. We report results from the first 3 patients dosed with VX-880 with at least ~1 year of follow-up.
Methods and Materials: The trial has 3 parts: Part A where 2 patients are enrolled sequentially and receive half the target dose, Part B where 5 patients are enrolled sequentially and receive the target (full) dose, and Part C where 10 patients are enrolled concurrently and receive the target dose. Following a single infusion of VX-880, patients are monitored for safety and tolerability (as assessed by adverse events [AEs] and clinical laboratory assessments), fasting and stimulated C-peptide, HbA1c, glycemic variability, interstitial glucose by continuous glucose monitoring, and exogenous insulin dose.
Results: Among the first 3 patients dosed with VX-880 and at least 1 year of follow up, 2 are insulin independent. Following VX-880 infusion at half target dose, Patient 1 in Part A, who was taking 34.0 units insulin/day and had HbA1c of 8.6% with 40.1% time-in-range (TIR) at baseline, became insulin independent at Day 270 and remains insulin independent at Month 18 (HbA1c 5.2%; 97.7%TIR). Patient 2 in Part A, who was taking 25.9 units insulin/day and had HbA1c of 7.5% with 35.9% TIR at baseline, had improved HbA1c (6.2%) and TIR (61.7.%) with a daily insulin dose of 27.8 units/day at Month 12. Patient 2 subsequently withdrew from the study for personal reasons. Patient 3, the first patient in Part B, received the full target dose of VX-880. This patient, who was taking 45.1 units insulin/day and had HbA1c of 7.6% with 53.8% TIR at baseline, became insulin independent at Day 180 and remains insulin independent at Month 12 (HbA1c 6.0%; 96.8 % TIR). VX-880 has been generally safe and well tolerated at both doses; the majority of adverse events (AEs) were mild or moderate in severity and there were no serious AEs considered related to VX-880. The safety profile was consistent with the immunosuppressive regimen and the perioperative period.
Conclusions: These results demonstrate that a single infusion of stem cell-derived islets (VX-880) can restore insulin production and glucose regulation, leading to insulin independence in patients with T1D. Based on this, VX-880 has the potential to be a functional cure for patients with T1D. Part B is fully enrolled and multiple additional patients have been dosed with the target dose. Longer-term and updated data from all patients dosed in Part A and Part B will be presented at the conference.
