One of the companies generating a lot of hope on the diabetes research front is San Diego-based ViaCyte, making significant headlines as it marches toward what it describes as a “functional diabetes cure.”
Specifically, ViaCyte is working on a method of “reprogramming” human stem cells to grow into new insulin-producing cells, to be implanted into a patient’s pancreas housed in a tiny device. That would allow the organ to basically do the work of a healthy pancreas, regulating glucose levels with insulin so that a person with diabetes would no longer need to inject or dose insulin externally.
ViaCyte came into the spotlight recently after early clinical research showed promising results about the safe and effective use of this implanted device in the body.
“The data from these papers represent a significant scientific advance,” said Dr. James Shapiro, study lead author and director of the Islet Transplant Program at the University of Alberta, Canada. “It is the first reported evidence that differentiated stem cells implanted in patients can generate meal-regulated insulin secretion, offering real hope for the incredible potential of this treatment.”
Shapiro doesn’t say that lightly, as he’s one of the world’s leading experts on diabetes islet cell encapsulation, who pioneered the landmark Edmonton Protocol in the late 1990s. So, his faith in ViaCyte’s early research is encouraging, to say the least.
Read on to learn all about ViaCyte’s method and device, and the specifics of their latest research findings.
Known as Novocell before being renamed back in 2010, the company ViaCyte has been on the scene studying this type of encapsulation work for at least a decade.
Their idea is simple: Regenerating islet cells normally within the pancreas, by placing them into a small device implanted in the body, to grow more cells and dispense insulin as needed to regulate glucose levels.
This notion of regenerative medicine has seen ups and downs over the years, but ViaCyte has been slowly but surely moving forward. They got the regulatory green light from the Food and Drug Administration (FDA) in 2014 to begin clinical trials on their Band Aid-style encapsulation device, and in recent years their clinical studies have shown exciting promise.
DiabetesMine has talked with ViaCyte leadership many times through the years, including former CEO Paul Laikind, who in 2019 talked about how the company learned through initial human trials that what it had considered its second-generation model was actually better suited to be released as a first-generation product.
PEC-Direct: For higher risk diabetes cases
Now, ViaCyte’s PEC-Direct technology is first up in its development pipeline.
The technology itself is about half the size of a credit card and loaded with millions of pancreatic cells derived from stem cells. These cells can further develop into beta cells, which produce insulin and lower blood sugar, and alpha cells, which make glucagon, a hormone that raises blood sugar.
It would require immunosuppressant drugs and would be limited to about the 10 percent of type 1 diabetes (T1D) patients who are at the highest risk for hypoglycemia unawareness and extreme hypos, and other more severe complications.
PEC-Encap: Reducing the need for immunosuppressant drugs
The now-second-gen product called “PEC-Encap” would in theory allow ViaCyte to “tone down the foreign body response” — meaning less reliance on immunosuppressant drugs — making it suitable for use among the broader T1D and even insulin-using type 2 diabetes population.
“We started with PEC-Encap because we thought it could be ready out-of-the-box, and if that were the case, then we would not need PEC-Direct. But we could have it in our back pocket if needed,” CEO Laikind told DiabetesMine. “As we learned, we made some important findings and saw that it would be better to do it differently.”
Laikind explained that what they discovered in the clinic was an aggressive foreign substance response to the device components that didn’t allow the cells to thrive or function properly, so they paused the research trial to study and improve it more before resuming.
ViaCyte has also been collaborating with leading global materials science company W.L. Gore & Associates on a newer, more effective membrane that would coat the Encaptra cell device to counter the foreign substance response in the body.
This is the technology that’s been on display throughout the Diabetes Community and at big diabetes conferences through the years, generating a lot of excitement — even though it’s still a long way off. Most recently, it’s being featured in a diabetes documentary called “The Human Trial” that is expected to be released soon.
Note that ViaCyte isn’t the only company developing this type of encapsulation technology, and it’s also not the only one working on stem cell-derived cell research. Massachusetts-based Vertex has also been in the news in 2021 for its exciting early research success, with its first patient looking to be ‘functionally cured.’
But ViaCyte has been around doing this the longest and usually captures the most interest from those watching anything related to diabetes cure research.
On Dec. 2, 2021, ViaCyte published findings from its first-in-human phase 1/2 ongoing study in patients with T1D who regularly experience severe hypoglycemia episodes. Those preliminary peer-reviewed findings were published in the journals
The Cell Reports Medicine paper reported on 17 patients implanted with ViaCyte’s PEC-Direct device, who showed positive C-peptide levels as early as 6 months post-implant in some cases.
Additionally, initial data showed that these stem cell-derived pancreatic cells can be separated and reproduced as a scalable, renewable source of insulin-producing pancreatic islet cells — meaning they can get around the hurdle of generating more of these cells to implant in patients.
Findings also showed that in 15 patients, researchers observed that the cells had matured into insulin-producing islet cells 6 months after implantation. They also detected a rise in C-peptide levels after patients ate a meal, indicating functional insulin production. That research also showed implanted patients spent 13 percent more time in target glucose range, with some able to reduce the amount insulin needed.
“We’re highly encouraged by our initial success and are now implanting larger numbers of cells in more patients,” said Dr. David M. Thompson, principal investigator of the Vancouver study published in Cell Stem Cell. “We believe we’re on the right track toward developing therapies that can improve the lives of millions of people with T1D worldwide.”
What’s fascinating about ViaCyte is that it’s not just focusing on these two encapsulation devices and the many related issues that come along with that type of research. But also, as DiabetesMine reported in 2018, ViaCyte has been dipping its toes into the gene editing space.
ViaCyte has been collaborating with international biopharm company CRISPR Therapeutics to use gene editing to supplement islet cell encapsulation, which has the potential to protect the transplanted beta cells from the inevitable immune system attack that normally kills them off. This would, of course, eliminate the need for patients to take immunosuppressant drugs, which can have major drawbacks and have been a big barrier to cell implantation to date.
In November 2021, the two companies announced that Health Canada had approved their request to start using an experimental gene-edited immune-evasive therapy known as VCTX210, and begin enrolling patients in this first-in-class clinical trial. The first patient was dosed with the experimental treatment, per an early 2022 news release from the two companies.
“We are excited to work with CRISPR Therapeutics and ViaCyte to carry out this historic, first-in-human transplant of gene-edited, stem cell-derived pancreatic cells for the treatment of diabetes designed to eliminate the need for immune suppression,” Dr. Shapiro in Canada said, as he’s a clinical investigator in the trial. “If this approach is successful, it will be a transformative treatment for patients with all insulin-requiring forms of diabetes.”
Even in the initial stages, many looked to this as an exciting early step on the path to creating a stem-cell derived product that can resist immune system attack — basically by reworking the cells’ DNA to evade that attack.
The JDRF has praised this research, with the organization’s vice president of research, Dr. Sanjoy Dutta, saying: “This is an enormous step forward in alignment with JDRF’s vision to bring insulin independence to people with type 1 diabetes without the need for immunosuppression.”
It’s all very exciting, if only in the research phase, and that’s where we have to pause for a breath.
What is a ‘functional cure’ or ‘biological cure’ for diabetes?
In some ways, ViaCyte’s collaboration with CRISPR expands on the notion of whether we’re talking about a “cure” here at all. That “C” word is always a controversial one in our Diabetes Community, particularly whether it prevents T1D in the future or basically nixes it for those who’ve already been diagnosed.
ViaCyte’s approach has often been referred to as a “functional cure,” because it would only replace the missing insulin cells in the body of a person with T1D, but not address the autoimmune roots of the disease.
But working together, both CRISPR and Viacyte can potentially do both, to pursue a true “biological cure.”
ViaCyte may well be our knight in encapsulated armor. The company has appropriately offered cautious hope.
Too often, though, it’s the media messengers — or at least the headline writers — who often get carried away when talking about anything cure-related.
That “hope vs. hype” balance is nothing new for our D-Community, so we trust you all to keep your expectations in check, while appreciating that the research progress from ViaCyte is quite encouraging these days.
As Dr. Jay Skyler lays out in his 2017 Diabetologica article on the subject, “hype and hope are not mutually exclusive.”
Here is Dr. Skyler’s list of cautions on issues faced when conducting and reporting studies in type 1 diabetes:
- success of studies in rodents poorly translates to success in humans
- incomplete understanding of the pathogenesis of T1D in humans
- the disease may be uniform in rodent models but heterogeneous in humans
- need for appropriate expectations in both the scientific community and people with T1D
- importance of rigorous application of the scientific method
- limitations of interpretation of small pilot studies that are under-powered
- progress is often slower than desired
- there are often new unanticipated issues that need to be solved on the road to success
- inherent conflict in wanting to report success while acknowledging limitations
- the entire scientific enterprise (investigators, funders, journals) needs to take responsibility for tempered and realistic reporting
In closing, our message would be to embrace the hope, but mind the hype appropriately. And in the meantime, keep calm and carry on, Wayward Pancreas Peeps.