Diabetes developments – by Simon O’Neill
This week Simon rounds up the latest technologies, medicines and treatments.
Ultra Rapid Insulin
Eli Lilly have announced that they are ending their licensing agreement for ultra-rapid-acting insulin BioChaperone Lispro. The company that developed this insulin, Adocia, has stated that they will seek a new partner while continuing preparations for a Phase 3 trials program.
This doesn’t necessarily mean that Lilly are no longer interested in ultra-rapid acting insulins as apparently they have more than one in development and they may be choosing to focus their resources on another solution to deliver insulin more rapidly.
BioChaperone Lispro had completed Phase 2 trials, with positive results presented at last year’s American Diabetes Association meeting, but was awaiting a decision from Lilly on whether or not it would advance the insulin into Phase 3. Up until last December Lilly had highlighted the phase 3 initiation for BioChaperone Lispro as a key event for 2017.
Meanwhile, Novo Nordisk have got European approval for their ultra-fast acting insulin, Fiasp (fast acting insulin aspart) and plan to launch it in some European countries early this year.
Fiasp is the same as insulin aspart (NovoRapid) but in a new formulation, in which two new inactive ingredients have been added to ensure earlier, greater and faster absorption, thereby providing earlier insulin action.
Research showed that it had a similar effect when taken up to 20 minutes after eating as NovoRapid taken before meals – however, it is still recommended that it should be taken before eating to get the best effects.
Clinicians and patients have been calling for faster acting insulins for some time, particularly for use in insulin pumps, so that they can more closely mimic the action of endogenous insulin.
The artificial pancreas
Although an artificial pancreas was conceivable in the early 2000s, there seemed to be too many obstacles in the way to actually bring something to market. But last year the FDA approved the first hybrid closed-loop system, Medtronic’s MiniMed 670G system, after only a three month review. The system is expected to be available in the US soon and will likely be rolled out elsewhere during 2017.
However, Medtronic is by no means the only player in this field, and at least five other companies have plans to bring their systems to the market over the next two years. This is a great example of research working with industry as all these systems rely on an algorithm to analyse the blood glucose results from the CGM and to use that analysis to decide what to do in terms of giving or suspending insulin delivery from the pump. The algorithms have been designed by university teams but are now being used by companies to create working artificial pancreases.
Tandem is working on both a predictive low glucose suspend model and a hybrid closed loop system. The first means that the algorithm can predict when blood glucose levels are likely to go low and to suspend insulin delivery to prevent this from happening. The second system will adjust background levels of insulin automatically to keep blood glucose levels in a target range, but the person with diabetes will still need to give bolus doses of insulin to match meals.
The low suspend model is being trialed this year with a release date expected in the US at the end of 2017. The hybrid closed loop system is also being trialed this year with an expected US release in early 2018. Both systems will use the t:slim X2 pump and the Dexcom G5 CGM system.
Another company, Bigfoot, are also planning a major trial of their Biomedical Smartloop Automated Insulin Delivery Service in summer 2017 with an expected submission to the FDA in early 2018. This system works alongside a smart phone, with an expectation that bolus doses can be controlled by an app on the phone, rather than having to go directly to the pump. The user also won’t necessarily have to count carbs, but can just say what the meal is going to be and the technology will determine the required insulin dose.
Beta Bionics are taking a slightly different approach with their iLet Bionic Pancreas – a dual hormone system. As well as giving insulin to bring blood glucose levels down, this system also contains glucagon, which can be given to bring blood glucose levels up, if a low is anticipated or occurs.
Their major trial is expected to start later in 2017, again with a submission to the FDA expected in mid 2018, though this may be for an insulin only version, with a longer time scale anticipated for the dual hormone system, as they are still working on a long term stable form of glucagon.
Animas are at a slightly later stage with their Hypo/Hyper Minimiser system but, interestingly, at this stage it seems that they are the only company looking at children as young as two to be included in trials. A final product is likely in 2019.
The Insulet Omnipod Horizon system is also unique as it will use the Omnipod patch pump – so will be the only AP system that is tubeless. They will also be focusing on the paediatric population (as well as adults) but probably won’t come to market much before the end of 2019.
None of the systems in the pipeline are fully automated, so the user will still have to bolus insulin to match meals and occasionally to bring a very high glucose level down and, of course, there will still be the hassle of pump changes, CGM calibration etc. But evidence so far has shown that these algorithms can really help keep blood glucose more tightly in a target range, particularly at night, so not only reducing hypos and hypers but also lowing HbA1c.
In addition to these commercial systems, there is still a lot of activity in the DIY fields, with several algorithms being in the public domain, using existing technology. Other algorithms are also being devised to help people who don’t use insulin pumps, to give them better advice on changing doses, depending on what their blood glucose levels are doing.
Voluntis’ Insulia, which got FDA approval at the end of last year, is software that will suggest changes in insulin doses for people with Type 2 diabetes on basal insulin alone. The system uses finger prick blood glucose readings to suggest appropriate changes to insulin doses. This app will launch in 2017 in the US and in Europe.
So, does this mean an end to multiple daily injections? The answer is definitely ‘no’ for several reasons. The technology behind AP systems has been around for some time – it’s the algorithms that are new – and we already know that not everyone wants to be on an insulin pump or be attached to a CGM full time – in fact some studies have shown that up to 18% of people discontinue pump use for a variety of reasons.
In the US, where these systems have been available for many years, only about 30% are on pumps and 10-15% on CGM. That is partly down to choice – but also down to cost.
In the UK relatively few adults are able to access either pumps or CGM because of cost – and the new systems are likely to cost at least as much as existing technology – and perhaps even more because of the algorithms and the fact that they can do more. So while the AP advocates are talking about these systems as the next best thing to a cure, the cynics out there are asking ‘can we afford this technology?’ and ‘will those who chose not to use it, get left behind?’
There is also a need for much better education in T1D, which is already lacking in the UK. Although an AP system can do a lot, the user still needs a good knowledge of diabetes and how it is affected by day to day living, as well as an understanding of what CGM data means and how to make appropriate decisions.
Prof Kath Barnard said at the ATTD meeting that this has to be about the right technology, at the right time, for the right person. If we don’t get that right, then we may actually just increase diabetes distress for some people.
We will need more data on clinical and cost effectiveness if we are to make these new systems more widely available to more people. But the direction of travel is exciting and will certainly be life changing for those who can access AP technology in the near future.
A new medical app to help manage gestational diabetes is to be rolled out to several NHS Trusts over the next year. The app, one of several, is currently being trialed in four Oxfordshire hospitals but has been picked up by a commercial company to expand its reach.
The app, called GDm-health, enables women to seamlessly send all their blood glucose readings to their diabetes midwife. This enables midwives to quickly assess who may need more attention, as well as who is managing well. A two year long trial within an NHS Trust found that the system reduced the number of patient visits by 25%, better for the clinic and the individual mums to be.
The group that developed the technology, the Oxford University Institute of Biomedical Engineering, has been approached by other trusts wanting to use this, but the research group doesn’t have the resources to deliver further trials. This is where Drayson Technologies has stepped in to set up an Oxford based team to commercialise the app. This team will manage the rollout of the technology – as well as two other apps – at up to four NHS trusts within a year, with a long term plan to eventually offer these products to the entire NHS.
Startup companies at the ATTD meeting
The Advanced Technologies and Treatments for Diabetes (ATTD) meeting is an opportunity for researchers and companies to discuss new projects that are in development. Not all of these will make it into routine diabetes care, but the breadth of ideas being worked on is fascinating.
Evopump is an interesting technology which shows great promise. This is a flexible, bandage like pump which is designed to deliver one or more medications subcutaneously. It is made from a soft, thin, and flexible material to enable precise delivery of injectable drugs. It is a disposable device which can be worn for three days and comes with a separate hand held controller.
There isn’t actually any ‘pump’ mechanism and the device is driven by electrolysis. A small electrical current creates gas bubbles in the electrolyte which consequently creates pressure to push the drug through the cannula into the skin. Tests so far have shown that this mechanism can deliver very accurate dosing.
As it can store more than one type of drug, the company are starting to see if they could develop it as an insulin pump, delivering both insulin and glucagon, with the longer term potential of developing an artificial pancreas with this as the delivery mechanism.
Jupiter Technologies are working on the development of a non-invasive blood glucose monitor using a radio frequency spread spectrum. This is at an early stage but they have successfully been able to measure a range of glucose levels in the lab between 2 and 22 mmol/l. They are now undertaking further tests to see whether they can achieve the same degree of accuracy when there are other compounds present (as would be the case in a blood sample).
If they can get that to work, the next stage will be testing on humans. Many companies have tried different approaches to non-invasive monitoring, none of them, so far, successful so this is still quite a long shot, but one that would be greatly welcomed by people with diabetes.
Sensulin are developing a once daily long acting insulin that responds to the levels of glucose in the blood using something called ‘Agglomerated Vesicle Technology’. This creates a ‘grid’ of liposomes – tiny molecular sacs of lipids (fats) which can enclose drugs or other substances. In this instance they are formed around the insulin. These liposomes gradually break down and release the insulin but as glucose levels rise, these liposomes break down more rapidly thereby responding to the rising glucose by releasing more insulin.
At present this is still in the proof of concept phase with a study in rodents. As well as being suitable as a background insulin, the company are also exploring the use of this to replace bolus insulin as well, releasing insulin as glucose levels rise after a meal.
Theranova are trying to develop a peritoneal artificial pancreas, though this is in the very earliest stages of development. Insulin pumps have already been developed that can be placed inside the body, which seem to work well as there is more rapid insulin absorption there. This company is trying a slightly different approach to develop a single implant that can both measure glucose and deliver insulin. Very much a ‘watch this space’ moment.