PEC-Direct™ – Treating High-risk Type 1 Diabetes
The PEC-Direct™ product candidate delivers stem cell-derived PEC-01™ pancreatic progenitor cells in a device designed to allow direct vascularization of the cells, and is being developed for patients with type 1 diabetes (T1D) that are at high risk for acute complications, including coma and death.
The PEC-01 progenitor cells are designed to mature in to human pancreatic islet cells, including glucose-responsive insulin-secreting beta cells, following implant.
Who would benefit from treatment with the PEC-Direct product?
High-risk T1D patients are those who have hypoglycemia unawareness (HU; characterized by a reduced or absent ability to detect the symptoms commonly associated with low blood sugar), recurrent severe hypoglycemic episodes (SHEs), and/or extreme glycemic lability (also commonly referred to as “brittle diabetes”). It is estimated that approximately 10% of patients, or over 100,000 people with T1D in the United States, have such high-risk diabetes that despite their best diligence with blood glucose monitoring, insulin use, and other pharmaceutical approaches, they are at constant risk of SHEs which can lead to hospitalization and even death.
If successful, PEC-Direct treatment will reduce or eliminate the incidence of HU and SHE, and stabilize glycemic lability. It is anticipated that T1D patients receiving the PEC-Direct implant will also no longer require insulin administration or glucose monitoring, effectively amounting to a functional cure. Like an organ transplant, the PEC-Direct product will be used in conjunction with immune suppression to prevent immune rejection of the implanted cells. While the requirement to take immune suppressive medications with PEC-Direct introduces some risk, it is expected that for the high-risk T1D patients, the benefit of a functional cure will far outweigh the potential risks.
The advantages of the PEC-Direct product
Transplant with cadaver islets has demonstrated the tremendous potential of cell therapy as a treatment for high-risk T1D patients. The direct vascularization of the implanted cells with islet transplant, and as designed for the PEC-Direct product candidate, can result in a robust, long-acting implant. However, a scarcity of suitable donated cadaver pancreases has limited the availability of this procedure. Since an unlimited supply of PEC-01 cells can be produced, PEC-Direct effectively presents the opportunity to treat all high-risk insulin-requiring patients.
Allowing the patient’s cells to have direct access to implanted cells through direct vascularization means that autoimmune and alloreactive responses may be activated, so patients receiving the PEC-Direct product are expected to need immunosuppressive medications, similarly to those who receive organ transplants. It’s expected that the Edmonton Protocol medications, utilized for patients receiving islet transplants, will also be protective for PEC-Direct. The Edmonton Protocol has demonstrated a very good safety profile to date.
Another advantage over cadaver islet transplant is the ability to terminate treatment should the need arise. Because the implanted cells are expected to remain in place, it is anticipated that it will be straightforward to remove the device and cells from patients if required.
Because PEC-Direct patients must be on immunosuppressive medications, there will be a certain risk/benefit scenario for this treatment, and as a result ViaCyte has identified high-risk T1D patients as the most appropriate candidates for the PEC-Direct product candidate. ViaCyte believes that pursuing the PEC-Direct product candidate will be the most rapid way to get the invaluable PEC-01 cell replacement therapy to those who need it most, the high-risk T1D
How does the PEC-Direct product compare to islet transplants?
The high-risk T1D patients for whom the PEC-Direct product is being developed are those who might also be eligible for cadaver islet transplants, a procedure that has proven to be highly effective but suffers from a severe lack of donor material as well as other procedural limitations. ViaCyte believes that PEC-Direct could overcome the limitations of cadaver islet transplant by providing an unlimited supply of cells, manufactured under quality-controlled cGMP conditions, and delivered by a safer, more optimal, route of administration. While cadaver islets are delivered into the liver, the PEC-Direct product candidate is intended to be implanted under the skin in a manner that would allow for removal of the product should that be deemed necessary. This approach is more straightforward and represents a significant safety advantage relative to delivery into the liver.
Next Steps for PEC-Direct
ViaCyte has completed the critical IND-enabling activities for the PEC-Direct product candidate, including GLP safety evaluation in animals. The PEC-Direct IND and CTA, regulatory submissions required to allow clinical trials to proceed, in the US and Canada respectively, were accepted by the FDA and Health Canada in May 2017. The clinical investigation of PEC-Direct is now underway. More information on the clinical trials can be found at clinicaltrials.gov.