ViaCyte announced the U.S. Food and Drug Administration (FDA) has allowed the company's Investigational New Drug Application (IND) for the PEC-Direct product candidate, a novel islet cell replacement therapy in development as a potential cure for patients with type 1 diabetes who are at high risk for acute life-threatening complications. ViaCyte has also received a No Objection Letter from Health Canada, providing clearance to proceed with the clinical trial of the PEC-Direct product candidate in Canada as well.
ViaCyte is proceeding to initiate an open-label clinical trial to evaluate the PEC-Direct product candidate for safety and definitive evidence of efficacy. In the coming year, the company expects to enroll approximately 40 patients at multiple centers, including the University of Alberta in Edmonton, the University of Minnesota, and UC San Diego. The primary efficacy measurement in the trial will be the clinically relevant production of insulin, as measured by the insulin biomarker C-peptide, in a patient population that has little to no ability to produce endogenous insulin upon enrollment. Other important endpoints to be evaluated include injectable insulin usage and the incidence of hypoglycemic events.
"The loss of insulin-producing beta cells leads to type 1 diabetes, making it an ideal target for cell replacement therapy," said James Shapiro, MD, PhD, FRCSC, Director of the Clinical Islet Transplant Program, University of Alberta. "Islet transplants from scarce organ donors have offered great promise for those with unstable, high-risk type 1 diabetes, but the procedure has many limitations. With an unlimited supply of new islets that the stem cell-derived therapy promises, we have real potential to benefit far more patients with islet cell replacement."
The PEC-Direct product candidate delivers stem cell-derived pancreatic progenitor cells, called PEC-01 cells, in a device designed to allow direct vascularization of the cells in the device. After implantation, these cells are expected to proliferate and mature to human islet tissue including well-regulated beta cells producing insulin on demand. The direct vascularization of the implanted cells is expected to allow for robust and consistent engraftment but will necessitate the use of maintenance immune suppression therapy.
The PEC-Direct product candidate is being developed for type 1 diabetes patients who have hypoglycemia unawareness, extreme glycemic lability, and/or severe hypoglycemic episodes. It is estimated that about 140,000 people in Canada and the U.S. have such high-risk type 1 diabetes. In addition to providing an unlimited supply of cells for implantation, the PEC-Direct approach has the potential to provide other advantages relative to cadaver islet transplants such as delivering a more consistent product preparation under quality-controlled cGMP conditions, with a more straightforward and safer mode of delivery.
PEC-Direct is one of two product candidates in clinical development to treat patients with diabetes. ViaCyte's PEC-Encap (also known as VC-01) product candidate delivers the same cell therapy as PEC-Direct but uses a proprietary device called the Encaptra Cell Delivery System that is designed to protect the cells from the patient's immune system. The PEC-Encap product candidate is being developed as a transformative therapy for all patients who require insulin to control their disease. Early clinical evidence with the PEC-Encap product supports the potential of the replacement cell therapy approach. However, the clinical results also indicate that further work to optimize the performance of the PEC-Encap product is required. ViaCyte recently announced a collaboration with W. L. Gore & Associates focused on modifying the Encaptra device to improve engraftment in patients.
ViaCyte's PEC-01 cells are the biological component of both PEC-Direct and PEC-Encap product candidates. PEC-01 pancreatic progenitor cells are manufactured from pluripotent stem cells and are designed to further differentiate and mature after implantation, not only to fully functioning insulin-producing beta cells, but also to the other endocrine cell types that make up the normal healthy human pancreatic islet. This mixture of pancreatic cell types is expected to produce on-demand the necessary insulin, along with other hormones that are important for the regulation of glucose in the blood including glucagon, somatostatin, and amylin.