Two-year Data from ViaCyte's STEP ONE Clinical Trial Presented at ADA 2018
Two-year data show survival of mature endocrine islet cells when PEC-Encap is well vascularized; encouraging non-clinical data on modified Encaptra Cell Delivery System may support resuming trial enrollment in 2019.
SAN DIEGO, June 23, 2018 /PRNewswire/ -- ViaCyte, Inc., a privately-held regenerative medicine company, today announced two-year data from Cohort 1 of the ongoing Safety, Tolerability, and Efficacy of VC-01™ (PEC-Encap™) Product Candidate in Type One Diabetes (STEP ONE) clinical trial. The PEC-Encap combination product candidate consists of stem cell-derived pancreatic progenitor cells (PEC-01) encapsulated in a delivery device called the Encaptra® Cell Delivery System. The results indicate that the PEC-Encap product candidate, delivered at a sub-therapeutic dose, has to date been safe and well tolerated. The Encaptra Cell Delivery System appears to protect the implanted cells from allo- and auto-immune rejection and the patients from sensitization.
Although consistent and robust engraftment was limited in this study, results showed that when engraftment did occur, viable mature insulin-expressing endocrine islet cells were formed. In some cases, insulin-expressing cells persisted for up to two years after implantation, the longest time point investigated in the study. Details from the STEP ONE trial will be provided in an oral presentation today at 4:00 p.m. ET at the American Diabetes Association's (ADA) 78th Scientific Sessions in Orlando.
Howard Foyt, M.D., Ph.D., Vice President, Clinical Development and Chief Medical Officer at ViaCyte said, "PEC-Encap holds the promise of being a functional cure for all patients with type 1 diabetes. The preliminary results from the STEP ONE clinical trial suggest that we are on the right track. In addition to being safe and well tolerated thus far, the results indicate that when successful engraftment occurs, the implanted cells survive, proliferate, and mature to cells capable of producing insulin and other regulatory hormones. The study has also shown that the Encaptra Cell Delivery System protects the cells from rejection by the patient's immune system."
STEP ONE is an open-label Phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of the PEC-Encap product candidate. Cohort 1 of the study, which was designed to deliver a sub-therapeutic dose of cells, has enrolled 19 patients with established but stable type 1 diabetes. Patients were implanted subcutaneously with two different PEC-Encap unit sizes: VC-01-250 and VC-01-20. The larger VC-01-250 units are used primarily to evaluate safety and tolerability, and eventually efficacy, while VC-01-20 units are smaller "sentinels" that are removed at various time points throughout the study for histological and other analyses. PEC-Encap units were explanted at approximately 1, 2, 4, 8, 12, 16, and 104 weeks (two years). After all units were removed, patients continued in a follow-up observational study. Efficacy will be evaluated in Cohort 2.
Including 12-week and two-year time points, data show the following:
Safety and Tolerability: The PEC-Encap product candidate appears to be safe and well tolerated in the study thus far. The majority of adverse events (AEs) were related to surgical procedures and/or post-operative care. No off-target growth has been observed by ultrasound or histology.
Immunology Assessment: The Encaptra Cell Delivery System appears to protect against allo- and auto-immune rejection and sensitization. Immune function tests showed no donor-specific antibodies, no increase in auto-antibody titers, no tolerance or sensitization to donor cells, and no increase in lymphocyte stimulation or antigen-specific CD8+ T cell frequency post-implantation.
Cell Differentiation and Survival: Although limited by low levels of engraftment due to a foreign body giant cell response, differentiation into endocrine islet cells was observed in both 12-week and two-year explants for both VC-01-250 and VC-01-20 units in regions where there was good host tissue integration and vascularization. Several two-year VC-01-250 explants had regions containing insulin-producing beta cells and glucagon-producing alpha cells, indicating that when engraftment occurs, cells can persist for long durations without the need for immunosuppression.
Encaptra Modifications: Building on insights gained during the study, ViaCyte is modifying the Encaptra Cell Delivery System to improve the potential for long-term engraftment. This work has yielded positive results in non-clinical models that, based on clinical experience, have been selected to reflect the response in patients.
"The STEP ONE clinical trial is the first of its kind and as such, has provided important new information for optimizing a stem cell-derived islet replacement therapy," said Robert R. Henry, M.D., Professor of Medicine, UC San Diego School of Medicine; Clinical Investigator, UC San Diego Altman Clinical and Translational Research Institute, and one of the principal investigators for the STEP ONE clinical trial. "To see the pancreatic progenitor cells survive and mature into endocrine cells in patients further supports the promise of this approach as a potentially transformative treatment for patients with type 1 diabetes."
"Facilitating robust and consistent functional engraftment is a key goal and the results evaluated to date from the clinical trial have provided important insights on strategies for achieving that goal. Based on the initial findings we have been busy working with our collaborators at W. L. Gore & Associates, one of the world's top materials science companies with expertise in medical device development and drug delivery technologies, to improve the Encaptra Cell Delivery System," said Paul Laikind, Ph.D., ViaCyte's President and CEO. "That collaboration has gone very well, and if the progress continues as expected, we plan to resume STEP ONE trial enrollment in 2019."
This work was supported in part by grants from the California Institute of Regenerative Medicine (DR1-01423; SP1-06513; AP1-08039; AC1-07764) and JDRF (IDDP 723434).
ViaCyte is a privately-held regenerative medicine company developing novel cell replacement therapies as potential long-term diabetes treatments to achieve glucose control targets and reduce the risk of hypoglycemia and diabetes-related complications. ViaCyte's product candidates are based on the derivation of pancreatic progenitor cells from stem cells, which are then implanted in durable and retrievable cell delivery devices. Once implanted and matured, these cells are designed to secrete insulin and other pancreatic hormones in response to blood glucose levels. ViaCyte has two product candidates in clinical-stage development. The PEC-Direct™ product candidate delivers the pancreatic progenitor cells in a non-immunoprotective device and is being developed for type 1 diabetes patients who have hypoglycemia unawareness, extreme glycemic lability, and/or recurrent severe hypoglycemic episodes. The PEC-Encap™ (also known as VC-01) product candidate delivers the same pancreatic progenitor cells in an immunoprotective device and is being developed for all patients with diabetes, type 1 and type 2, who use insulin. ViaCyte is also developing immune-evasive 'universal donor' stem cell lines, from its proprietary CyT49 cell line, which are expected to further broaden the availability of cell therapy for diabetes and other potential indications. ViaCyte is headquartered in San Diego, California. The Company is funded in part by the California Institute for Regenerative Medicine (CIRM) and JDRF. For more information on ViaCyte, please visit www.viacyte.com and connect with ViaCyte on Twitter and Facebook.