The PEC-Direct product is being developed for adults who are at high risk of acute complications related to their type 1 diabetes (T1D). High-risk T1D patients are those who have severe hypoglycemic episodes (SHEs), extreme glycemic lability, and/or hypoglycemia unawareness (HU), which can lead to hospitalization and even death. Approximately 10-15% of people with T1D may have a combination of HU (characterized by a reduced or absent ability to detect the symptoms commonly associated with low blood sugars), extreme glycemic lability (also commonly referred to as “brittle diabetes”), and/or an unacceptable incidence of SHEs. More than 100,000 people in the US have high-risk diabetes.
For these T1D patients, PEC-Direct could represent a functional cure. Like an organ transplant, PEC-Direct will be used in conjunction with immunosuppression to prevent immune rejection of the implanted cells. While the requirement to take immunosuppressive medications with PEC-Direct introduces some risk, it is expected that for these T1D patients, the benefit of a functional cure will far outweigh the potential risk. If successful, PEC-Direct treatment is expected to reduce or eliminate the incidence of SHEs, extreme glycemic lability, and HU.
To learn more about ViaCyte’s product candidates, including the PEC-QT program, see product pipeline.
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 very 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 islet transplants by providing an unlimited supply of cells, manufactured under quality-controlled cGMP conditions, and delivered by a potentially 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 self-contained manner that would allow for removal of the product should that be deemed necessary.
The PEC-Encap and PEC-Direct clinical trials are designed to help answer these questions. In pre-clinical studies, ViaCyte has tested product candidates for the animal’s lifespan, or about a year, and they have remained functional up to that point. Data presented at ADA 2018 from the STEP ONE study showed that, when engraftment did occur, viable mature insulin-expressing endocrine islet cells were formed and persisted for up to two years after implantation, the longest time point investigated in the study.
To deliver ViaCyte’s stem cell-derived islet cell replacement therapy, the company is taking three distinct approaches to addressing the patient’s immune system. These approaches distinguish the clinical-stage PEC-Direct and PEC-Encap product candidates, as well as the preclinical PEC-QT program, from each other. See our product pipeline for an explanation of the differences.
In addition to the autoimmunity that T1D patients have to diabetes-related antigens, the vast majority of recipients of the ViaCyte’s islet cell replacement therapies will have alloimmunity to the delivered cells. That is, the PEC-01 cells in PEC-Encap and PEC-Direct are human cells, but because they are not the patient’s own cells, they also need to be protected from an alloimmune response, just as organ transplants are.
In the case of PEC-Direct, the cells will be protected similarly to an organ transplant, with chronic immunosuppressive medications. The same types of immunosuppressive medications that are currently used with cadaver islet transplants, also known as the “Edmonton protocol,” may be used in the clinical trial of PEC-Direct. Because PEC-Direct is expected to require pharmacological immune suppression, it is intended only for high-risk T1D patients.
In the case of PEC-Encap, the cells are protected using a macroencapsulation device, called Encaptra. Preclinical studies provided evidence that cells encapsulated with ViaCyte’s devices are protected from autoimmunity, as well as alloimmunity. Preliminary observations from the STEP ONE clinical trial of PEC-Encap suggest that the Encaptra device is performing its immunoprotective role in humans as well: no evidence of auto- or allo-immune rejection or sensitization has been observed in patients implanted with the PEC-Encap product candidate.
For the PEC-QT program, genes encoding proteins that are involved in activating immunity are edited in the CyT49 source cells, so that the resulting implanted cells will be ‘immune evasive’ and should not evoke an immune response.
The development of innovative medical products is a highly regulated endeavor that involves establishing safety and efficacy over time. While we are committed to developing our product candidates in a timely fashion, our number one consideration is the well-being of the patients. We are unable to say with certainty how long it will be, assuming development is successful, before one of our products is available outside of clinical trials. We appreciate your continued patience and support as we go through the necessary steps of product development.
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