The artificial pancreas represents a dramatic improvement over existing approaches to management of diabetes, but Sernova Corp. of London, Ontario, is intent on going one better on conventional device technology. The company recently presented the results from an early phase study of its Cell Pouch device with pancreatic islet cells to a major medical conference, and the results suggest that the Cell Pouch with islets will pass the safety bar and may prove efficacious for several measures, including glycemic control.
Sernova presented data from the phase I/II study of the combination of the Cell Pouch and transplanted pancreatic islet cells to an audience at the 2019 meeting of the International Pancreas and Islet Transplantation Association, describing the results of a single patient with type 1 diabetes. That patient also is dealing with severe hypoglycemic unawareness, and the patient experienced no adverse events, even as she lost 12% of her body weight during the course of the evaluation.
Hypoglycemic events down 88%
Over a period of two weeks, the patient enjoyed a reduction in hypoglycemic events of nearly 88%, and blood tests indicated that the pouch had stimulated C-peptide and insulin at 90 days in a mixed-meal tolerance test. The performance of the device was corroborated for stabilized glycemic control parameters by a continuous glucose monitoring system made by Medtronic plc. of Dublin.
Sernova has been on the trail of that elusive target for some time. The company made its presence known to investors at a conference in 2012, at which point the Cell Pouch was already the carrier of choice for pancreatic cell islets. Sernova had pulled in more than $4 million in investor and grant funds at that point, although the hope at the time was that it could bring in another $10 million to nudge its research further along.
In the meantime, the company met a number of milestones toward viability as a small med-tech company, including receipt of a patent from the U.S. Patent and Trademark Office for the Cell Pouch and related transplant technologies in 2015. The FDA gave the company an investigational device exemption (IDE) for the use of the Cell Pouch in diabetes in 2017, although Sernova was already at the time forming plans to use the device for treatment of hemophilia. The Juvenile Diabetes Research Foundation was on board with the effort to develop the Cell Pouch for type 1 diabetes with a bolus of $2.45 million by then to support the IDE study.
Philip Toleikis, Servnova's CEO, told BioWorld that the Cell Pouch is about 25% smaller than a standard business card, and is manufactured from polymers into a scaffold designed to permit vascularization. The idea behind the pouch's design and materials is to prevent fibrosis – a common occurrence for device implants – to ensure a sufficient level of vascularization to allow the islets to do their job.
Toleikis said the device is designed with the expectation that it will be placed under the skin in the area of the waist, where it will not be noticeable thanks to its diminutive dimensions. The pouches are only a few millimeters thick, and more than one pouch would be implanted, albeit at sufficient distances to ensure the islets are responding to a systemic rather than local signal. The device is implanted in a surgical suite for the purposes of the IDE study, but Toleikis said that is not a complicated procedure and will be done on an outpatient basis so patients can head home on the same day.
When asked about device durability, Toleikis said animal studies have run to a year, but while he was reluctant to put a hard number on human use, he said that "our belief is that if we get good quality islets, we're expecting they will last for a very long time." He said the islets are obtained from cadavers and isolated via a process that is very well-characterized. "There have been no immune system reactions at all so far," he said, but the patients in this study are or will be on immunosuppression. Toleikis said Sernova is working on a technology that will handle immunosuppression locally rather systemically.
The FDA has authorized an enrollment of seven subjects in the study, and Toleikis said the company is focusing in part on the implant process to ensure the devices are correctly placed. He said seven patients should suffice to demonstrate to the agency that the concept is well-founded, and when asked when Sernova might approach the FDA with an application for a pivotal study, he said that "if all goes well, approximately in a year, maybe a little longer." In any case, he said, that application should arrive at the FDA sometime in 2020.
Toleikis pointed out that about 30% of patients with type 2 diabetes eventually need insulin, which suggests the market for the Cell Pouch plus pancreatic islets may be as large as 50 million in the U.S. alone. The market in the U.S. will be accessed mainly via private payers, although some Medicaid patients would obviously also qualify.
Sernova eyes North America, Europe
Jurisdictionally, the company has ambitions beyond the U.S., Toleikis, said, explaining that "we've already conducted a small first-in-human study in Canada." He said Sernova has an open regulatory document on file with Health Canada, but a pivotal trial will have to cover several geographic areas if the company's ambitions are to be fulfilled. "We would prefer to do something that would be a combined European/U.S./Canadian study," Toleikis said.
Toleikis said that in addition to the hemophilia A indication, the company is also developing the Cell Pouch as a treatment for hypothyroidism, the subject of a research grant. And while the news about the use of the device in type 1 diabetes might seem to present little threat to current FDA-approved technologies, he said that "even this first patient, I feel, is a significant advancement in this field."