Diabetes developments – by Simon O’Neill
In a regular blog series, Simon O’Neill, Diabetes UK’s Director of Health Intelligence and Professional Liaison, rounds up the latest diabetes news.
This week Simon rounds up the latest technologies, medicines and treatments.
Several papers reported a study by Oramed Pharmaceuticals who announced that they had positive top-line results from their Phase IIb study, designed to evaluate the safety and efficacy of their oral insulin capsule (ORMD-0801) in patients with T2D. (A Phase IIa trial has also been published by Novo Nordisk on their oral insulin product OI338GT.)
This is something of a breakthrough though still in early proof of concept stages. The reason oral insulin hasn’t worked before is because insulin is a protein chain, and proteins get digested in the stomach and intestine, both by stomach acid and by protease. Even if it survives that far, insulin also then has to be absorbed through the intestine wall, which proves problematic.
Oramed have tackled this problem by developing a ‘shield’ for the drug capsule which is a pH sensitive enteric coating. This means that the capsule dissolves only once it is in the small intestine. At this stage, the tablet also contains protease inhibitors, which limit the effect of protease and protect the insulin from attack. Finally, they have developed an absorption enhancement process, which allows the insulin to cross the intestinal membrane and enter the bloodstream. They also use a large dose of insulin so that it doesn’t all have to survive the journey through the gut.
The 28 day, double blind, randomized study of 180 people with T2D showed a statistically significant decrease in average night-time glucose, with those on the drug achieving a 6.47% lower mean blood glucose over the 28 nights. The study additionally demonstrated a good safety profile with no drug related serious adverse events. Although not a dramatic difference (if the average CGM night time blood glucose had been 9mmol/l then this would mean a reduction to 8.4mmol/l) the aim of the trial was to show safety and that the insulin was absorbed and functional.
The next stage of development will be to conduct larger Phase III trials and also to begin to look at insulin profile. This was used as a replacement for overnight, long acting insulin – but is it possible to develop a rapid acting oral insulin that could replace day time injections? There will be many issues to overcome – particularly with regard to doses, which can vary greatly from person to person and, in an individual, from meal to meal or day to day. Currently accurate doses of 0.5 units of insulin can be given by injection, whereas the pill delivered 8mg or 16mg of insulin. Obviously not all of this is absorbed – and much like with inhaled insulin, a new dosing system will need to be developed and tested. (With inhaled insulin 8mg was equivalent to about 22 units of injected insulin – but as this is a different delivery method, we can’t equate the two).
However, the company seem to be positioning this as an add on oral therapy for those with T2D not achieving great control on other oral medicines, in which case the accuracy of dosing is probably not as critical as it would be in managing T1D.
But this is a breakthrough in proof of concept at the very least, and the company are convinced that they can crack the problem. It may just take a while yet.
GlaxoSmithKline and Alphabet’s Verily Life Sciences, formerly Google Life Sciences, have launched a new company, Galvani Bioelectronics, dedicated to the development of bioelectronic medicines.
And what might they be, I hear you ask? Bioelectronics is, as it sounds, the unlikely combination of traditional pharmaceuticals with the bioengineering field, which aims to tackle long term diseases using miniaturised, implantable devices that can modify electrical signals that pass along nerves in the body. The belief is that many illnesses lead to irregular or altered impulses and that these could be overcome, or suppressed, by bioelectronics.
Some smaller companies are already making progress in this field. EnteroMedics got FDA approval for their device last year which is designed to reduce appetite in the very obese. This is an implant placed around the vagus nerve, which blocks signals from the nerve, making the individual feel less hungry and feel full for longer. Another company, NeuroPace, recently began marketing the RNS System, a device for people with epilepsy that can’t be controlled with medication. This monitors brain activity, identifies unusual activity and then stops seizures using electric impulses.
GSK has been working in this area since 2012, trying to target diseases such as arthritis, diabetes and asthma. Galvani will be trying to develop implants, the size of a grain of rice, or even smaller, that can be attached directly to nerves to treat diseases, with the hope of either enhancing or replacing drugs. The first, and perhaps biggest challenge, will be finding clinical proofs of principle in a variety of disorders including T2D, based on existing evidence from animal tests. Scientists believe the precise wavelength and frequency of the electrical pulses will be crucial to their success and may need to change constantly to have the desired effect.
Early prototypes of bioelectronics are currently being tested in rats. Glaxo is planning initial human trials for three major long term conditions next year. The company has not yet announced the areas it’s looking into, but many people believe that arthritis and T2D will be high up the agenda.
This certainly isn’t going to be a simple fix, with one of the biggest problems being that we still don’t know which neurons control which organ functions, or how to finely adjust their behaviour.
They also need to develop small enough power sources that can last for many years; micro-computers within the implants which are able to read and analyse biological signals and then adjust the electrical output appropriately ; and materials that won’t degrade over time or harm fragile nerves.
But the technology is getting there. Vestibular implants already exist which help patients whose sense of balance has been damaged by disease. Placed in the inner ear, they measure the movement of the head and convert that information into electrical pulses. These are then fed directly into nerve branches and the brain via electrodes, delivering information directly into the nervous system. Other scientists have also demonstrated the feasibility of “self-powered nano-devices,” which generate their own electricity from tiny vibrations in their environment.
And researchers announced in August that they have developed an edible battery made from the skin pigment melanin, which means it is non-toxic and can be used safely in the body. Melanin’s suitability comes from its ability to bind and unbind metallic ions – a process that powers standard batteries. The first battery can produce enough energy to power a 5 milliwatt device for up to 18 hours.
It is difficult to see exactly how this could benefit T2D at present, but that is where further research is needed to see if there are areas of the nervous system we could tap in to, to improve T2 diabetes control.
Fitbit, the market leader in the health wearables field, is beginning to move more in to direct healthcare. The company currently produce a range of wearables that track steps taken, heart rate and sleep quality as well as wifi enabled weighing scales that measure BMI and body fat percentage. But the company are now trying to use the data that is generated by the devices in more clinical settings, as well as developing partnerships with healthcare providers, pharma companies and medical device manufacturers.
The idea is that the lifestyle changes that Fitbit’s devices help their users to establish are exactly the same as are needed both to prevent many diseases but also to manage them most effectively, T2D being a good example
This may also mean developing new devices. Fitbit currently have one activity tracker than can also help you with a fitness workout by giving you step-by-step instructions and coaching.
But it isn’t all plain sailing. Currently Fitbit’s products are classed as ‘general wellness devices’ and require no regulation, as they make no health claims but just track actions and activity. However, if the company are to start making health claims or to help with diagnosis or treatment, then this may require regulation. The FDA has already said that it will treat ‘mobile medical apps’ in a different way. These are health apps that are intended to be used as an accessory to a medical device or to transform a mobile platform into a regulated medical device. So if a mobile app is intended for use in performing a medical device function (i.e. for diagnosis, treatment or prevention of a disease) it is classed as a medical device, regardless of the platform on which it is run. This will require a more rigorous assessment and regulation.
The Fitbit is currently being investigated in over 200 clinical studies in conditions ranging from breast cancer to heart disease, so the chances are the devices will end up being regulated in future.