Initial Clinical Evaluation of VC-01TM Combination Product—A Stem Cell–Derived Islet Replacement for Type 1 Diabetes (T1D)
Authors: HENRY ROBERT R. , PETTUS JEREMY , WILENSKY JON , SHAPIRO A.M. JAMES , SENIOR PETER A. , ROEP BART , WANG RICHARD , KROON EVERT J. , SCOTT MICHAEL , D'AMOUR KEVIN , FOYT HOWARD L. 
Published: June 2018

VC-01 is a novel cell replacement therapy being developed as a potential long-term diabetes therapy to more effectively control glycemia, reduce hypoglycemia risk and mitigate diabetes-related complications. VC-01 is derived from directed differentiation of human embryonic stem cells to pancreatic progenitor cells, which are loaded into a durable, retrievable delivery device and then implanted subcutaneously. Once implanted and matured, the cells secrete insulin and other islet hormones in response to blood glucose levels. The delivery device is immunoprotective to implanted cells. VC-01 is currently being evaluated in a 24-month open-label, dose-escalating Phase 1/2 study in T1D patients with minimal insulin-producing β-cell function. Cohort 1 has evaluated product at a subtherapeutic dose to assess initial safety and tolerability and establish implantation techniques. To date, 19 subjects have been implanted and evaluated throughout implantation duration until final product explant. Product has been safe and well tolerated; adverse events have been relatively minor and generally related to the surgical procedure. The delivery device has provided protection against the host adaptive immune system with no evidence of allogeneic or autoimmune rejection or sensitization based upon a sensitive panel of immune function tests. No off-target growth of donor cells has been detected. The potential for prolonged cell survival has been demonstrated, as long as 24 months, but has been inconsistent among subjects and primarily limited by a foreign body response to the device component. Positive immunohistochemical staining for pancreatic islet cell markers NKX6-1, insulin, and glucagon has been observed. These preliminary results demonstrate the immune-protective nature of the encapsulation device and safety of this human stem cell-derived product, but also indicate the ongoing requirement for optimization of the host response to device materials.

Disclosure
R.R. Henry: Consultant; Self; Abbott, Alere Inc., AstraZeneca. Research Support; Self; AstaReal. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Bristol-Myers Squibb Company. Advisory Panel; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Hitachi, Ltd.. Advisory Panel; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Johnson & Johnson Services, Inc.. Research Support; Self; Lexicon Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Advisory Panel; Self; Merck & Co., Inc.. Consultant; Self; Merck & Co., Inc.. Research Support; Self; Viacyte, Inc.. Consultant; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. J. Pettus: Advisory Panel; Self; Sanofi, Novo Nordisk Inc.. Consultant; Self; MannKind Corporation. Advisory Panel; Self; Insulet Corporation. Consultant; Self; Senseonics. J. Wilensky: None. A. Shapiro: Consultant; Self; Viacyte, Inc., Protokinetix. P.A. Senior: Consultant; Self; Abbott, AstraZeneca. Research Support; Self; AstraZeneca, Prometic Life Sciences Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; AstraZeneca, Merck & Co., Inc., Abbott. Research Support; Self; Viacyte, Inc. B. Roep: Consultant; Self; Viacyte, Inc.. Research Support; Self; Viacyte, Inc. R. Wang: Employee; Self; Viacyte, Inc.. Stock/Shareholder; Self; Sanofi. E.J. Kroon: Employee; Self; Viacyte, Inc. M. Scott: Stock/Shareholder; Self; Viacyte, Inc.. K. D'Amour: None. H.L. Foyt: Employee; Self; Viacyte, Inc.. Stock/Shareholder; Self; Viacyte, Inc..