- We visited Drs. Ed Damiano and Steven Russell (of BU and MGH, respectively) at Camp Joslin to follow the latest bionic pancreas summer camp study in patients 6-12 years old. The device again received rave reviews from campers.
- In addition to the ongoing multi-center study, four pre-pivotal bionic pancreas studies are planned for 2015, including a chronic glucagon exposure study, a blood glucose set point study, an alcohol tolerance clamp study, and an additional pediatric study in newly diagnosed patients.
For the second consecutive summer, our team had the privilege of visiting the Joslin Clinic’s long-running camp for children with diabetes – Camp Joslin – as Drs. Ed Damiano and Steve Russell conducted the second installation of their summer camp studies of the bionic pancreas. Tucked away in rural Massachusetts, the study included only six boys – a smaller enrollment relative to last year’s 16 given the challenges of recruiting a much younger population (ages 6-12). Each participant served as his own control, meaning five days of usual care at camp were compared to five days of 24-hour closed-loop control wearing the bionic pancreas. Three boys at a time wore the bionic pancreas, which still includes two Tandem t:slim pumps (insulin and glucagon), a Dexcom G4 Platinum sensor and transmitter, and an iPhone 4S running a control algorithm. A similar girls’ study took place two weeks earlier and enrolled 13 campers, for a total of 19 participants in this round of the study. As a reminder, the 2013 camp study was published in NEJM simultaneous with Dr. Russell’s oral presentation at ADA 2014.
A key change from last summer’s study was less reliance on remote monitoring, a testament to greater FDA comfort with the system – this year, nurses did not receive continuous glucose data from the campers and were only alerted when blood glucose levels remained below 60 mg/dl for 15 minutes, which prompted a fingerstick blood glucose measurement; campers were treated for hypoglycemia anytime a fingerstick blood glucose measurement was less than 80 mg/dl. Similar to last year, campers were not really restricted in their behavior; they participated in camp activities ranging from street hockey to full-court basketball, ate as they pleased, and slept in shared cabins. In line with the 2013 camp studies’ publication in NEJM, data from this year’s studies is tentatively anticipated around early summer 2015.
As a reminder, the MGH/BU team is currently testing the Bionic Pancreas in an 11-day multicenter home study (n=40 total, ten each at MGH, UMass, UNC, and Stanford); results from the first two patients were shared at FFL 2014 in July. Meanwhile, there are four studies slated for 2015: a chronic glucagon exposure study over ~12 months; a blood glucose set point study (~1H15) to examine different algorithm targets; an alcohol study to assess the PK/PD profiles of glucagon; and an additional pediatric study in newly diagnosed patients. The team’s goal is still to conduct a pivotal study throughout 2016 (n=100s, several months) and submit the PMA to the FDA in 1H17. The aim continues to be an FDA-approved platform on the market in late 2017 , when Dr. Damiano’s type 1 son will be head to college. Between now and then, key milestones – aside from collecting the clinical data – will include development of a dual-chambered pump and a stable glucagon for use in the final approved system.
For a snapshot of our learning-filled trip, check out the pictures below!
- After only two days of use, the bionic pancreas was already receiving a rating of “six stars out of five” from the young study participants; those not on the technology admitted to being just a bit jealous. Receiving this feedback on only the second day of the trial was particularly telling, given that the device is designed to adapt and improve its performance over time, peaking around the third or fourth day. A highlight of our visit was hearing the reaction to the scheduled pre-dinner blood glucose checks – one comparison between campers revealed that those on the bionic pancreas were ~150 mg/dl while those on usual care were ~200 mg/dl, much to the rueful admiration of everyone in the cabin. Upon hearing the timeline for a 2017 commercialization, one bionic camper revealed to us, “I can’t wait that long!”
- One criticism of the device from the campers – consistent with last year – was the bulkiness of the prototype system (two Tandem t:slim pumps and an iPhone controller hardwired to a Dexcom G4 Platinum receiver). Despite the new fanny pack-esque pouch designed by TallyGear, the kids noted that sleeping was particularly uncomfortable given the wires trailing over them. However, they all readily admitted that they would buy the device as is, two separate pumps and iPhone controller included! On a positive note, wearers of the bionic pancreas did not cite many issues with infusion sets falling out – a point of concern in last year’s study. This might have been due to the much lower temperatures this summer that seemed to reduce the frequency with which the adhesive gave way. Dr. Russell also noted that the final device will use an infusion set with two steel cannulas; the team thinks these will be more reliable than the plastic cannulas used in the studies to date because it is not possible for them to kink.
- At Friends for Life 2014, Dr. Damiano made it fairly clear that the final pivotal study device is currently being built in collaboration with his “industrial collaborators” (although he didn’t specify who those collaborators were). It will be a fully integrated device with CGM input, a dual-chambered pump, and algorithms all contained within a single handheld unit (i.e., it will not run on an iPhone like the current research device does). The product is expected to use a single snake bite infusion set with a dual-lumen catheter.
- Aside from the younger population, the biggest difference relative to last year’s camp study was a significant reduction in monitoring. Nurses were blinded to campers’ CGM data, such that they only received an alert when a patient’s blood glucose was below 60 mg/dl for 15 minutes, which prompted a fingerstick blood glucose measurement; campers were treated for hypoglycemia anytime a fingerstick blood glucose measurement was below 80 mg/dl. Last year, monitoring staff could see the continuous glucose data in the central control room. Dr. Russell emphasized that the reduction in monitoring is a step toward the elimination of monitoring altogether. As we understand it, the monitoring reduction stems from greater FDA comfort with the system.
- In response to the Bluetooth and cellular connectivity issues faced in 2013, the researchers tweaked the control algorithm running on the iPhone (eliminating the “scrolling feature”). As a reminder, last year’s devices experienced connectivity problems about 4-7% of the time, possibly degrading glycemic control. Drs. Damiano and Russell are hoping for improved connectivity and patient outcomes this time around. Of course, this won’t be an issue in the pivotal study device, as everything will be integrated into one product.
- Dr. Russell shared his vision of ideal glycemic control, noting that he would be “thrilled” to achieve blood glucose values in the 145-155 mg/dl range while avoiding hypoglycemia entirely. He emphasized that the goal of the device is not to achieve normal non-diabetic blood glucose values. Indeed, though it is widely believed that lower blood glucose values are better, Dr. Russell emphasized that DCCT data do not support that perspective – the reduced risk of complications associated with lower blood glucose values appears small once patients achieve an A1c of ~6.5% (though he acknowledged that the one exception might be a modest increase in cardiovascular risk). In Dr. Russell’s opinion, the additional risk of severe hypoglycemia that comes with very low A1c levels is not justified.
- Consistent with this goal, a blood glucose set point study is at the top of the researchers’ to-do list in 2015. As a reminder, the bionic pancreas is designed to target a set blood glucose value (e.g., 100 mg/dl) that determines how much dysglycemia the device tolerates and how aggressively the algorithm brings patients back into range. Dr. Russell noted that increasing this set point (e.g., 130 mg/dl) may reduce time spent under 60 mg/dl without greatly increasing average blood glucose levels. He stressed that such a modification would be of particular benefit to patients with low mean blood glucose levels on the bionic pancreas, but who still experience some hypoglycemia. The crossover study will assess glycemic endpoints at various controller set points (e.g., 100 vs. 115 vs. 130 mg/dl) to determine whether the range of mean glucose values on the bionic pancreas can be made even smaller and hypoglycemia can be further reduced. It will also look at total daily insulin and glucagon dosing at the different target levels.
- We’d note that some have criticized the bionic pancreas for achieving tight glycemic control at the expense of aggressive insulin dosing combined with excessive glucagon rescue. In particular, we’ve heard critics point to the supplemental 2013 Summer Camp/Beacon Hill experimental data published in NEJM (e.g., in some patients, over 1 mg of glucagon was used per day, often with microdoses in close proximity to insulin). Certainly, there is potential for real harm depending on how the algorithm is tweaked. The ongoing multi-center trial (11-day experiments), pre-pivotal studies, and the longer and larger pivotal study in ~2016 should reveal much more about the safety of the team’s insulin/glucagon approach.
- Another 2015 study will examine long-term glucagon exposure over 12 months – the biggest hurdle is a realistic study design and participant adherence. Dr. Russell outlined the challenge of conducting a 12-month study in a population without diabetes that still has an incentive to adhere to protocol and bear the hassle of wearing a glucagon pump consistently – the parents of children with diabetes may be an ideal study population! The trial would have three treatment arms, exposing subjects to varying amounts of glucagon, based on an algorithm that is programmed with the average glucagon use profiles of previous bionic pancreas users (Beacon Hill participants, for example) in order to make the glucagon administration profile realistic. We assume the study will test the stable Xeris glucagon, on which the MGH/BU team has done clamp experiments.
- A separate study will examine the impact of alcohol on glucagon PK/PD profiles. The researchers will manipulate participants’ blood alcohol content (BAC) via IV administration of ethanol. Dr. Russell noted that it actually builds on standard procedures for treating ethylene glycol and methanol poisoning. This should provide strong safety and risk-mitigation data to bring to the FDA – if commonly achieved levels of ethanol do markedly impair the effectiveness of glucagon perhaps patients could even alert the algorithm that they are drinking alcohol, and it could adjust dosing accordingly.
- Looking ahead, there are plans to evaluate the bionic pancreas in newly diagnosed and type 2 populations. These are likely further out in the timeline, though both would be important studies. As a reminder, the metabolic control study, which tested hybrid closed-loop control within days of type 1 diabetes diagnosis, did not show a significant preservation in C-peptide levels at one year.
- On the reimbursement front, Dr. Russell was relatively optimistic that payers will appreciate the benefits of the bionic pancreas. In his view, it is hard to imagine that payers would not be interested in the cost savings (e.g., fewer HCP and ER visits) that would result from the tight blood glucose control they have seen, despite the higher upfront costs. Many have criticized the dual-hormone approach as too expensive, though Dr. Russell hypothesized that glucagon expenses will likely decrease as its use becomes more common.
- As background, a compelling Helmsley Charitable Trust video summarizes the 2013 Summer Camp study of the Bionic Pancreas – the five-minute video is captivating, engaging, and provides a most valuable overview of the study and how transformational the technology could be.
Pictures from Camp Joslin
The youngest “bionic camper” – a six-year-old! – was thrilled to test drive the bionic pancreas
Daily calibration of the bionic pancreas with Dr. Russell
The Close Concerns team with another bionic superstar, posing with his “Go Bionic” carrying case
-- by Varun Iyengar, Melissa An, Adam Brown, and Kelly Close