ViaCyte FAQ (frequently asked questions)
ViaCyte is a clinical-stage company developing transformative cell therapy products for diabetes. Below are answers to commonly asked questions.
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 ViaCyte’s clinical trials can be found at clinicaltrials.gov.
The PEC-Encap product candidate is a more challenging product candidate for a number of reasons. While it has functioned well in certain preclinical models, there was no human experience with similar products to consider. As it has the potential to be a functional cure for all T1D patients, PEC-Encap was tested in the clinic first, starting with subtherapeutic dosing. Recognizing that the clinical evaluation could indicate that PEC-Encap requires further optimization, ViaCyte was also developing the PEC-Direct product candidate in parallel, as a therapy for T1D patients that are at high risk of acute complications. With PEC-Direct ViaCyte hopes to get the islet cell replacement therapy to those with the most urgent unmet medical need, the soonest.
ViaCyte is making a great deal of progress with PEC-Encap, demonstrating that it has thus far been safe and well-tolerated, that the Encaptra device is immunoprotective (no evidence of allo- or auto-immune rejection or sensitization), and that long-term cell viability is feasible, ableit not sufficiently reliably using the current Encaptra device configuration. While ViaCyte is not yet ready to move to the Phase 2 stage of clinical development with the PEC-Encap product candidate, the team continues to work towards that goal.
In the meantime, the observations with PEC-Encap are informing the development of PEC-Direct as an important first-generation product for the T1D patients with the highest unmet medical need. With multiple product candidates being investigated and developed, ViaCyte has a greater chance of helping diabetes patients that can potentially benefit from the islet cell replacement therapy technology as soon as possible. Given the potential therapeutic value of this novel beta cell replacement therapy, we feel it is important to get it to the patients with the most urgent unmet medical need as quickly as safely possible.
ViaCyte has informally described preliminary results from the STEP ONE clinical trial of the PEC-Encap (also known as VC-01) product candidate. The company has been evaluating the PEC-Encap candidate at a sub-therapeutic dose to evaluate safety and develop the procedures for successful implantation. The early, preliminary data shows that:
- Thus far, the treatment appears to be safe and well tolerated.
- The Encaptra device appears to be protecting the implanted cells from both allogeneic and autoimmune rejection and sensitization as it was designed to do.
- Pancreatic progenitor (PEC-01) cells within PEC-Encap can engraft, vascularize, and differentiate into pancreatic islet tissue including beta cells (insulin-producing cells) for at least twelve weeks after implantation.
These results demonstrate that the company is making progress translating to patients the promising results that were established in preclinical models. These early findings are important milestones in the development of a “functional cure” for type 1 diabetes as they show that the essential aspects of the product concept can translate to the clinic under appropriate conditions.
While these results are promising, we believe certain product and/or procedural improvements will be required for PEC-Encap to be proven effective. We are working on ensuring a robust engraftment and reducing patient-to-patient variability before advancing clinical development of PEC-Encap to a fully therapeutic dose.
The STEP ONE clinical trial for the PEC-Encap (a.k.a. VC-01) product candidate has enrolled approximately 20 patients and based upon initial findings, the team has decided to pause enrollment in order to make modifications to the Encaptra cell delivery device that are expected to improve product performance. The Gore-ViaCyte joint development team is actively working on such modifications.
The clinical trial for the PEC-Direct product candidate began enrolling patients in 2017. The PEC-Direct product candidate delivers the same PEC-01 pancreatic progenitor cells as the PEC-Encap product candidate but in a device designed to allow direct vascularization of the cells. PEC-Direct is being developed for patients with high-risk type 1 diabetes, and we also expect that learnings and advances with Gore will facilitate improvements in the PEC-Direct device.
The goal of this research agreement is to cooperatively establish new methods of effectively delivering cell therapies. Gore has over 40 years of expertise in medical device development as well as previous research and development experience on cell encapsulation and implant programs for diabetes. They are the world leader in technologies related to implantable materials such as those used in the ViaCyte Encaptra® cell delivery device. Gore’s contribution to the material and design improvements of the Encaptra® delivery system is expected to support the reliable and robust long-term engraftment that is required for the PEC-Encap product to be most effective.
PEC-01 cells are a human cell product, developed and manufactured by ViaCyte, composed primarily of pancreatic progenitor cells. PEC-01 cells are manufactured from a line of pluripotent embryonic stem cells (called CyT49) using a carefully controlled directed differentiation process. The differentiation process is designed to yield a cell population that can mature into glucose-responsive insulin-producing cells. PEC-01 cells, as a result of the directed differentiation, are not pluripotent stem cells. In animal studies, after implantation PEC-01 cells have been shown to further differentiate and mature into pancreatic endocrine cells, including beta cells that secrete human insulin in response to increases in blood glucose.
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. The PEC-Direct product is being developed for the over 100,000 patients in the US alone who are at high risk of acute complications related to their type 1 diabetes (T1D). The PEC-01 progenitor cells are designed to mature into human pancreatic islet cells, including glucose-responsive insulin-secreting beta cells, following implant. High-risk T1D patients are those who have severe hypoglycemic episodes (SHEs), extreme glycemic lability, and/or hypoglycemia unawareness (HU). Like an organ transplant, PEC-Direct will be used in conjunction with immune suppression to prevent immune rejection of the implanted cells. If successful, PEC-Direct treatment is expected to reduce or eliminate the incidence of SHE, extreme glycemic lability, and HU. It is anticipated that patients receiving the PEC-Direct implant will significantly reduce or eliminate the need for insulin administration and/or glucose monitoring.
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 the PEC-Direct product candidate 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. This allows for ready removal of the product if necessary, a significant safety advantage relative to delivery into the liver.
There are T1D patients who, despite their best diligence with insulin and other pharmaceutical approaches, are at constant risk of severe hypoglycemic episodes (SHEs), which can lead to hospitalization and even death. Approximately 10-15% of people with T1D may have a combination of hypoglycemia unawareness (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. For these T1D patients, PEC-Direct could represent a functional cure. While the requirement to take immune suppressive medications with PEC-Direct introduces some risk, it is expected that for these T1D patients, the benefit of a functional cure will outweigh the potential risk.
Much product development work remains before PEC-Direct will be commercially available as a T1D treatment. 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. Although there are numerous factors to consider, if proven safe and effective in patients, it is possible that the PEC-Direct product for high-risk T1D patients could reach the market before the PEC-Encap product candidate.
The PEC-Encap, also known as VC-01, product candidate is a combination of two platform technologies:
(1) the PEC-01™ pancreatic progenitor cell therapy made by the directed differentiation (conversion to a target cell type) of an embryonic stem cell line, and (2) the Encaptra® cell delivery system used to deliver the cells to the patient and protect them from the patient’s immune system. The PEC-01 cell therapy is a population composed primarily of human pancreatic progenitor cells that, following implant, are expected to mature into the various cell types of the endocrine pancreas, also known as the Islets of Langerhans. The delivery device is a semi-permeable capsule made of medical-grade plastics, called the Encaptra® cell delivery system. A dose of PEC-01 cells loaded within the Encaptra device is collectively called the PEC-Encap (VC-01) product candidate.
The PEC-Encap product candidate represents an innovative marriage of these two platform technologies. Following implant, the Encaptra device is expected to integrate into the tissue and vascularize, meaning a dedicated blood vessel system will grow on the membrane of the PEC-Encap unit. At the same time, the PEC-01 cells are expected to mature into functional replacement human islets. By the time the mature beta cells are ready to sense glucose and release insulin (approximately three months following implant), the blood supply has developed to support and provide glucose to the cells, and to receive and carry insulin and other hormones produced by human islets away to the rest of the body where they are needed.
ViaCyte has early clinical demonstration of the principle of the PEC-Encap approach, having shown that engraftment and differentiation to beta cells is feasible based on analyses at three months post-implant. However, the clinical results indicated that further work is needed to improve tissue integration and vascularization of the Encaptra device. Based on results from the clinical investigation, device optimization efforts are ongoing to ensure robust and consistent engraftment with PEC-Encap before exploring higher doses to demonstrate efficacy. ViaCyte remains committed to the development of PEC-Encap, which is expected to be a potentially transformational therapy for the majority of people who use insulin to manage their diabetes, both T1D and T2D. However, for a number of reasons PEC-Direct development may advance more rapidly and make a major impact for the T1D patients at highest risk.
Both PEC-Direct and PEC-Encap are being designed as subcutaneous implants (that is, to be implanted under the skin). Both PEC-Direct and PEC-Encap deploy the PEC-01 pancreatic progenitor cells as the active ingredient that will provide the therapeutic effect. The main difference between the two product candidates is the nature of the device that will be used to deliver and retain the PEC-01 cells.
The PEC-Direct product candidate delivers the PEC-01 pancreatic progenitor cells in a non-immunoprotective device that allows direct vascularization of the cells. Studies have shown that direct vascularization can circumvent a foreign body reaction to the device. The PEC-Direct product is being developed for T1D patients who have severe hypoglycemic episodes, extreme glycemic lability, and/or hypoglycemia unawareness. Given the open nature of the device, patients implanted with the PEC-Direct product, as with organ transplants, are expected to require immune suppression. Thus, it is being developed to treat patients who are at high risk of acute complications related to T1D.
The PEC-Encap (VC-01) product candidate is expected to vastly expand the target patient population. In contrast to the PEC-Direct product, the PEC-Encap product delivers PEC-01 pancreatic progenitor cells in the Encaptra® immunoprotective device. This device prevents any interaction between the PEC-01 cells and the patient’s cells, thus protecting the PEC-01 cells from adaptive and autoimmune attack that would otherwise destroy them. The Encaptra Device incorporates a membrane to prevent this cellular interaction, so engraftment and function requires a vascular network to grow on the surface of the device to allow diffusion of nutrients. This requirement for vascularization on the surface of the membrane represents a higher engraftment challenge than that anticipated for the PEC-Direct product candidate. PEC-Encap clinical evaluation has been at sub-therapeutic levels in patients with T1D who have minimal to no insulin-producing beta cell function. The clinical trial remains open but enrollment is paused for the time being. Because the PEC-01 cells are fully encapsulated in PEC-Encap, we do not expect patients will need immune suppression.
The product candidates are designed to be surgically implanted in a minimally invasive manner. There are many possible implant locations, including placement under the skin (subcutaneously). One of the goals of the ongoing clinical trials is to identify the best implant locations and procedures.
The VC-01 product candidate consists of human cells delivered in a macroencapsulation device. It is considered a combination product that includes a device component but the active ingredient is the cell therapy and it is primarily regulated as a biologic agent. The “dose-ranging” VC-01 unit is about half the size of a business card and less than 1 mm thick.
The PEC-Encap and PEC-Direct clinical trials are designed to help answer these questions. In pre-clinical studies, we have tested a product candidate for the animal’s lifespan, which is about a year, and it has still functioned up to that point. The clinical trials are designed to evaluate the product candidates for as long as two years. For the majority of patients on optimized immune suppression therapy, cadaver islet transplants have remained effective for five years or longer.
To deliver the PEC-01 cell replacement therapy, ViaCyte is taking two distinct approaches to addressing the patient’s immune system. These approaches distinguish the PEC-Direct and PEC-Encap product candidates from each other.
In addition to autoimmunity that T1D patients have to diabetes-related antigens, the vast majority of recipients of the PEC-01-based islet cell replacement therapies will have alloimmunity to the delivered cells. That is, the PEC-01 cells are human cells, but because they are not the patient’s own cells, they will also need to be protected from alloimmune rejection, just as an organ transplant is.
In the case of PEC-Direct, the cells will be protected similarly to an organ transplant, with immune suppressive medications. The same types of immune suppressive medications that are currently used with cadaver islet transplants, also known as the “Edmonton protocol”, may be used in the PEC-Direct trial. 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. Pre-clinical animal studies with macroencapsulation devices, including the Encaptra drug delivery system, provided evidence that encapsulated cells 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 immune protective 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.
That depends on many factors, including patient enrollment and interim results. When available, we plan to publish and/or present the final results of the trial in an appropriate scientific forum.
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 both 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 the products are available outside of clinical trials. We appreciate your continued patience and support as we go through the necessary steps of product development.
For the past decade or so, two groups, ViaCyte Inc. and BetaLogics, a division of Janssen Biotech, Inc., have been pushing back the boundaries of science, making breakthrough advances in the development of a stem-cell derived cell replacement therapy for type 1 diabetes. The agreement to combine the intellectual property, expertise and other assets of BetaLogics with ViaCyte further strengthens our advanced program focused on insulin-dependent diabetes and solidifies our leadership in the field.