Miriam E Tucker

May 15, 2015

Nashville, Tennessee — The bihormonal "bionic pancreas" continues to perform well in clinical trials and could reach the US market by 2018.

In the opening plenary session here at the American Association of Clinical Endocrinologists' (AACE) 2015 Annual Scientific and Clinical Congress, the device's developer, Edward R Damiano, PhD, professor of biomedical engineering at Boston University, Massachusetts, summarized positive results from four recent outpatient clinical trials and described a proposed large, year-long pivotal trial that will be used to seek US Food and Drug Administration (FDA) approval.

"Bionic pancreas" is the name given specifically to the dual-chambered investigational device that comprises two separate pumps for delivering both insulin and glucagon, a continuous glucose monitor (CGM), and a control algorithm built into an iPhone app. Dr Damiano's team is now building a single integrated device that will incorporate all the different components. That device will be the one used in the pivotal trial, he explained during a press briefing.

In all four trials — two of which were presented at the American Diabetes Association (ADA) 2014 Scientific Sessions and simultaneously published in the New England Journal of Medicine — near-normal blood glucose levels were achieved in children and teens at a summer camp and in adults in real-world settings for 5 to 11 days at a time, with very low rates of hypoglycemia.

"What we're hoping is to bring technology that will not cure diabetes but will eliminate the management challenges to keep people safe, healthy, and out of harm's way until a cure is found," Dr Damiano said during his presentation.

Session moderator and American College of Endocrinology president Yehuda Handelsman, MD, medical director at the Metabolic Institute of America in Tarzana, California, told Medscape Medical News, "The use of glucagon is revolutionizing the whole concept of the artificial pancreas....[Dr Damiano] added the aspect of managing hypoglycemia. I think that's what's giving us a whole new confidence."

Dr Handelsman cautioned, however, that so far "these are very small studies in very willing people," which is why "we are very much anticipating this large phase 3 study."

Former AACE president Paul Jellinger, MD, clinical professor of medicine at the University of Miami, Florida, said, "It's clearly groundbreaking. What it tells me is how important insulin and glucagon are in the control of blood sugar....With these two hormones only, you're able to achieve exquisite control. I think the importance of this is that patients can forget about their disease."

Pushing Closer to Real-World Use

The two most recent studies were just completed in 2014 to 2015 and have not yet been published. In a 5-day trial at a summer camp in 19 preteens aged 6 to 11 years, the mean CGM blood glucose level with the bionic pancreas was 137 + 11 mg/dL, compared with 168 + 30 mg/dL when children wore their own pump and/or CGM device.

Time spent with blood glucose levels below 60 mg/dL (in the hypoglycemic range) was just 1.2% with the bionic pancreas vs 2.8% without. And time spent above 180 mg/dL — in the hyperglycemic range — was 17% vs 36%, respectively.

Insulin doses during the two periods were identical at 0.68 units/kg/day. "The device is using the same amount of insulin to achieve much better optimal glycemic control by distributing it in a much more optimal way. It's doing all this while reducing hypoglycemia," Dr Damiano explained.

The other new study was conducted at four US centers over a 10-month period and involved 38 adults aged 18 years and older. They wore the devices for 11 days with very little interaction between the investigators and patients, who lived at home and were able to freely move around. (In the previous study in adults, patients were escorted everywhere by a nurse.)

In the new study, mean CGM blood glucose levels were 141 + 10 mg/dL with the bionic pancreas vs 162 + 29 mg/dL without. Time spent below 60 mg/dL was 0.6% with the bionic pancreas vs 1.9% without and for above 180 mg/dL was 20% v 34%, respectively.

And, as in children, daily insulin doses were nearly identical in the two adult groups (0.66 vs 0.69 units/kg/day).

Pivotal Trial, FDA Involvement

Thus far, the pivotal trial that has been proposed to the FDA involves 480 patients as young as aged 13 years, of whom at least 100 will wear the bionic pancreas for a year.

At that point, co–primary outcomes measured will be HbA1c and percentage of time spent with blood glucose levels below 60 mg/dL. The same outcomes will be measured at the end of therapy in each study arm. There will be no remote monitoring.

When Dr Damiano was asked about timing, he said that he had hoped to complete the pivotal trial prior to the fall of 2017, because that's when his son — who was diagnosed with type 1 diabetes in late 2000 and is the inspiration for his career path — will be starting college.

However, now it probably will be pushed into at least early 2018, in part because the FDA will also have to approve a new indication for glucagon, which as of now is only a rescue medication and not indicated for chronic infusion, he explained. But, he said that the FDA has been very supportive and is working with his group to help expedite the process.

"FDA is highly incentivized to get this approved. They're working in a very collaborative way. They're seeing, literally, the pieces falling together," Dr Damiano told reporters.

And, he said, the FDA is also pushing for inclusion of younger children in the pivotal trial because it's likely that the devices will be used in infants and young children regardless of the indication. "FDA wants to push lower because they realize it would be used off-label. They want to test in as many people as possible."

Cost and Coverage

Asked about costs, Dr Damiano said that the dual-chambered device might cost more than a single-chamber pump, but that the CGM cost would be about the same and the entire system "would be in the ballpark" of the separate pump and CGM. Of course, he noted, the greatest expense comes from consumables — pump-infusion sites and sets and CGM sensors.

"Fortunately, most private payers reimburse for infusion sets and CGM. This does not work without a reimbursement model. That's a very big discussion that still has to happen," he said, referring to the fact that Medicare still doesn't cover CGMs. "The reimbursement part of this is not a trivial problem. We have to get private payers and [the Centers for Medicare & Medicaid Services] CMS on the same page."

Dr Damiano has received speaker honoraria from Eli Lilly, Dexcom, and Tandem Diabetes Care. Dr Handelsman has received research grant support, consultant honoraria, and fees from Boehringer Ingelheim, GlaxoSmithKline, and Novo Nordisk; research grant support and consulting fees from Amgen, Gilead, Merck, and sanofi aventis; research grant support from Intarcia Therapeutics, Lexicon, and Takeda; consultant/speaker fees from Amarin, Amylin, Janssen Global Services, and Vivus; and consultant fees from Halozyme Therapeutics. Dr Jellinger is on the speakers' bureau for Novo Nordisk, AstraZeneca, and Boehringer Ingelheim.

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