Progress continues on the so-called "biological cure," aka medical devices that can eventually be implanted under the skin to generate insulin as needed, eliminating the need for all the cumbersome blood sugar checks, carb-counting and insulin dosing required to date to control diabetes.
We've reported on these projects over the years, all expanding on the basic concept of islet cell encapsulation, as validated by the landmark Edmonton Protocol back in the late 90s.
One prominent player developing this type of cure-like device is the Canada-based clinical stage health sciences company Sernova, with it's implantable device dubbed the Cell Pouch, that's designed to allow for transplanted cells to be making insulin and ultimately eliminate the need for insulin injections and diabetes itself.
This month, as Sernova marks 10 years since its founding, it also celebrates a few significant milestones: the company has just recently begun human studies in Canada and has made headlines with news of JDRF financial backing, as well as a collaboration with the CTI Clinical Trial and Consulting Services to begin the investigatory regulatory review process with the US FDA to bring human clinical research here to the States.
OK, reality check: the process of in clinical trials, regulatory review, and commercialization will probably take at least 5 years before this product hits market (insert chuckle here about a cure always being 5 years away).
Still, Sernova's progress marks an important benchmark on this maco-encapsulation technology for PWDs (people with diabetes).
"It's extremely exciting to be at this point," says Sernova's President and CEO Dr. Phillip Toleikis. "While there have been previous attempts on implanted cell technologies and with encapsulation over the years, we've learned from all of that. We believe some groups may still be moving in the wrong direction, we believe we think we're getting over the hurdles that others have had."
We talked recently with Dr. Toleikis about the latest steps forward on Sernova's Cell Pouch, and are excited to share those updates. It's also worth watching this great video interview posted on TuDiabetes in early 2015 to learn more background on what the company's developing.
An Implantable "Pouch"?
As you can probably tell by the name, Sernova's product is a polymer "pouch" that's about the size of a business card, designed to be placed under the skin in any number of spots -- on the belly, leg, lower back, or around the shoulders. Therapetic cells, including Insulin-producing islet cells, are injected into the pouch once it's already implanted through a simple 15-minute surgical outpatient procedure.
Basically, the transplanted cells then grow inside this tissue-saturated natural environment and are vascularized to breath and live like normal insulin-making cells would in those without diabetes. And don't worry, Sernova is working on its own technology so anti-rejection drugs wouldn't be needed! The Cell Pouch has pores that keep out immune cells, but allow nutrients and insulin to move through the membrane, and so this integrated immune-suppression technology in the form of Sernova's proprietary Sertolin, means patients wouldn't need anti-rejection drugs.
While they don't yet know how long the Cell Pouch might last before it needs replacing, Toleikis hopes it could be five years or possibly even more.
Toleikis tells us Sernova's spent years doing extensive research on small and large animals for pre-clinical work on efficacy of the Cell Pouch. That research has shown two important things:
- Yes, the Cell Pouch can control BGs when placed under the skin in both small and large animal models.
- When looking inside the pouches after those studies, researchers have seen healthy islets sitting in tissue matrix that are highly vascularized and able to produce insulin.
“This is really important as it validates the Cell Pouch technology we have,” Toleikis said.
Sernova also worked with Health Canada (the FDA equivalent there) to do a first in-human test of Cell Pouch in patients in that country. That started a number of years ago in three PWDs with hypo unawareness. The Cell Pouch device was placed under the skin, with the islets placed into those implanted devices and over time the pouches were removed. The islets continued to thrive and be healthy in the body, Toleikis says, and there was no evidence of any immune system damage to the cells and the device itself was deemed safe for use prior to transplantation of the islet cells.
Two of the patients have now completed that study, and the third remains in the final stages with a Cell Pouch implanted under the skin for more than two years now, which is still healthy and functional.
No More Injections?
The Canadian current study was actually not about eliminating the need for insulin injections, but rather to ensure that the Cell Pouch is functional. Later phases will more specifically look at getting people off insulin, Toleikis says, although in study patients they've definitely seen improved A1Cs (possibly even from 8.5% to 6.5% in one individual), less insulin use and overall better BG management.
Next up is bringing their human clinical research here to the United States.
Once Sernova gets the green light from both the FDA and investigational review board (IRB), it will start the human study in the US. That will continue to look at device safety but will also look at islet dosing, i.e. how many islets can be injected into the Cell Pouch and whether a second dose is needed. Protocol development is part of this process -- figuring out what the standard will be in reviewing safety and efficacy -- measuring islet survival, C-Peptide levels, A1C, insulin use, glucose tolerance testing, and so on.
Sernova plans to enroll 7 patients in its first two-year study, and over time may ask for regulatory OK to increase that amount as they continue to build their knowledge base.
If all goes according to plan, Toleikis hopes to have early data by late 2017 to begin conversation with FDA on the regulatory approval to get this to market.
Naturally we wondered how this Cell Pouch is different from other, similar devices in development -- like the Diabetes Research Institute's BioHub and the band-aid sized ViaCyte Encaptra device, both being tested in humans here in the US.
Sernova's Toleikis describes it this way:
Most of the other "macro-encapsulation" devices, are themselves designed to protect the cells from the immune system, so that the cells are essentially "locked in place and separated from the natural tissue environment in bulk." He says that without the ability to have tissue directly integrated into the device, the body tends to wall off these devices with scar tissue, similar to the way the body isolates a splinter or a pacemaker -- a major disadvantage. Instead, Sernova's approach is to protect the cells from the inside.
Well, that certainly sounds reasonable...
Assembling the Puzzle
And it sounds like great progress is being made by Sernova! Of course, so much depends on funding -- especially for such a small company. Luckily, they're had some recent big wins.
In July 2016, Sernova announced securing a $2.45 million research grant from the JDRF to support a clinical trial at a yet-to-be-named transplantation center in the US. This adds to the JDRF support for Sernova's pre-clinical research in the past.
For that research, Sernova will focus on patients with hypo unawareness (PWDs who can't feel their low blood sugars), as they are ideal candidates for islet transplantations with a higher risk factor in needing this type of procedure, Toleikis tells us. Eventually they'll move to studying others with T1D, and people living with insulin-dependent T2D.
Also in early November, Sernova announced a collaboration with the Canada-based CTI consulting group to help move forward on FDA regulatory review process with all of this ongoing R&D. Simultaneously, Sernova is studying the sources for these new islet cells -- moving into the realm of stem cells that could be placed into the device, to regenerate naturally.
Put together, Toleikis tells us the puzzle is slowly being assembled to get the Cell Pouch developed, reviewed and eventually approved and to market, hopefully within that five-year window. But of course, it all depends on the clinical research and regulatory process.
"That (timeline) is pure speculation, but we are thrilled to be taking everything we have learned and bringing this all together," he said.
Toleikis says they are already exploring the cost and access aspects of the Cell Pouch that will materialize once this gets closer to commercialization. He doesn't plan for this to be "a million dollar device," though it's too early to speculate on reimbursement and exact pricing details.
"We are trying to change the standard of care for people with diabetes, to make life better than they've had it," Toleikis says.
Well, you can't argue with that!