196-LB: Stem Cell–Derived Islet Replacement Therapy (VC-02) Demonstrates Production of C-Peptide in Patients with Type 1 Diabetes (T1D) and Hypoglycemia Unawareness

Abstract

Patients with T1D exhibit a major loss in beta cell mass, associated with low or undetectable circulating markers of beta cell function. C-peptide serves as a biomarker used to assess the residual mass of functional insulin-producing pancreatic beta cells present in patients with T1D on insulin replacement therapies; this measurement is not confounded by exogenous insulin. Novel cell replacement therapies to address T1D, including VC-02 (PEC-Direct), have demonstrated the ability to control disease state and mitigate diabetes-related complications due to the absence of insulin and glycemic variability. In the current VC02-101 study, T1D patients were required to be C-peptide negative (during a mixed meal tolerance test) upon enrollment. Study participants received subcutaneous implanted VC-02 combination product containing pancreatic precursor cells (PEC-01 cells) derived from ViaCyte’s proprietary CyT49 pluripotent stem cell line. When effectively engrafted, these cells are capable of producing circulating C-peptide, as previously shown in rodent models, and now for the first time at clinically relevant levels in patients. Preliminary data for one patient implanted with the most current device configuration are presented through 6 months study duration. Stimulated C-peptide Cmax concentrations increased from 0.1 ng/mL (baseline) to 0.5 ng/mL (week 26), and AUC0-4hr increased from 0.225 to 1.775 ng x hr/mL. These results are corroborated by histology evidencing successful engraftment and cell survival. This effect was accompanied by an increase in time-in-range from 56 to 86% and reduction in HbA1C by 0.5%. Together, these data provide clinical proof-of-concept that further optimization of this therapy can result in a functional cure for T1D. Disclosure B. Keymeulen: None. D. Jacobs-tulleneers-thevissen: None. E. J. Kroon: Employee; Self; Viacyte, Inc. M. S. Jaiman: Employee; Self; Viacyte, Inc., Stock/Shareholder; Self; Viacyte, Inc. M. Daniels: Employee; Self; Viacyte, Inc. R. Wang: Employee; Self; Viacyte, Inc. D. Pipeleers: Board Member; Self; Beta-Cell NV. K. D’amour: Employee; Self; Viacyte, Inc. H. L. Foyt: Employee; Self; Viacyte, Inc., Stock/Shareholder; Self; Viacyte, Inc. Funding European Commission, Horizon 2020 (681070); California Institute of Regenerative Medicine (CLIN2-09672); JDRF (2011)