Given the rates of diabetes reaching ‘epidemic-proportions’, we figured it was time to have a better overview of biotech’s progress in the field. With some serious advances having been made in the treatment of the disease, we have to ask – how much further can biotech go in the treatment of diabetes? 

It is important to note the various complications that can arise from the disease, which has a series of serious co-morbidities. These can range from increased risk to infection, cardiovascular disease and even neuropathies (nerve damage across multiple tissues), each of which presents their own challenges to tackle.

So here’s a review of recent developments, including developments in insulin, the growing MedTech field and how cell therapy is also tackling the disease.

Diabetes Complications

Diabetes complications affected organs. Diabetes affects nerves kidneys eyes vessels heart brain and skin. (© Guniita / BigStock ID108710849)


Improving Efficacy of Insulin

Insulin was the first human recombinant protein to be approved on the market under the brand Humulin. It was initially developed by Genentech and marketed by Eli Lilly in 1982. This was a massive step forward to replace pig insulin and improve the life of diabetics worldwide. Since then, the recombinant insulin never stopped being improved.

Enhancing existing insulin treatments and Metformin have been the first line-of-treatments in tackling Diabetes (type I and type II respectively).

Although treatments vary between types, generally improving synthetic insulin is done by either increasing the absorption rate of synthetic insulin, new formulations (analogs – e.g. Lantus) or introducing biotechnological enhancers, such as BioChaperones. One example of the latter is the French biotech Adocia’s Biochaperne Lispro, which went on to be licensed by Lilly in 2014.

biochaperone_adocia_insulin_biotech_diabetes_review

Chaperoning proteins lengthens the protection the proteins have from enzymatic breakdown, permitting a longer effect, and therefore better glucose control when used for insulin. Biochaperone Lispro just completed a successful Phase I trial in Japan (Source: Adocia)

Additionally, other treatments include once-daily human analogues of the naturally occurring hormone Glucagon-Like Peptide-1 (GLP-1), which only stimulates the release of insulin when glucose levels become too high.

Many are working on these GLP-1 analogues as treatment for diabetes, particularly  type II – from Novo Nordisk’s Diabetes Care Unit to Sanofi (partnered with Denmark’s Zealand Pharma) and GSK etc.

The general principle here though is to combine these therapies with insulin analogues to maximise the effect. However, one of the main challenges in diabetes care is a sustainable and reliable drug delivery.

insulin_analogues_diabetes_review_glucose

Fig. 1 – Protein engineering has been used to produce variant forms of insulin, known as insulin analogues, with modified amino-acid sequences and improved pharmacokinetic properties. A number of insulin analogues have now been licensed for treatment, including rapid-acting forms for use at meal times and long-acting insulins for basal requirements.


MedTech: The Solution to Needle-Free Digitisation of Diabetes?

A big emphasis in the industry has been to find needle-free methods for delivery, given the obvious discomfort and hassle the repeated use of needles can cause (compliance, mistake of medication).

Improving Delivery

Over the last decade, an increasing number of drugs, from hormonal contraception to anti-smoking aids, have become available as transdermal drug delivery systems (TDDS). These are non-invasive patches that facilitate drug absorption through the skin.

nitto_transdermal_drug_delivery_skin_patches_diabetes_medtech-diabetes_review

The Japanese biotech Nitto is developing an example of a TDDS system called PassPort. However, the PassPort system is not yet being investigated for insulin delivery (Source: Nitto)

For insulin delivery, one example is Prometheon Pharma, which has developed the TruePatch, a multi-day basal insulin patch. Patches can also be problematic and irritating (e.g. cosmetically).

So another approach is the Intarcia implant from Boston (the Medici Drug Delivery System), partnered with the French pharma Servier. This is a futuristic matchstick-sized intra-dermal pump that has undergone three Phase III trials in conjunction with a GLP-1 agonist (exenatide).

itca_650_intarcia_diabetes_biotech_Review_delivery_glucose_insulin

Intarcia’s delivery pump system – ITCA 650 – is designed to be implanted into the arm for long-term needle free therapy delivery (Credit: Intarcia)

Ultimately, if approved, the ITCA 650 system (pump and GLP-1 formulation) would represent the first injection-free therapy capable of delivering up to a full year of treatment from a single device. Regulatory filing in the US is projected for later this year.

Replacing the Lancet

There’s also a whole range of monitoring tech out there designed to avoid the use of lancets to test glucose levels. These include GlucoSense (a spin-out company jointly formed and funded by NetScientific and the University of Leeds) that uses laser technology and NovioSense (a Dutch start-up in Nijmegen), which is a 15 mm-long metal coil that uses tear fluid to measure glucose.

needle_free_diabetes_biotech_review_chronic_disease_cure_monitor_glucose

On the other hand, Gluco-Wise is a new product from MediWise (in London), which is also an optical reading device designed for the ear-lobe. There is also the hotly discussed Google Lens being developed in conjunction with Novartis. Trials are due to start for the lens this year (read more via IEEE Spectrum), however, it’s not so clear whether this is a lot of ‘hot air’, as one ex-Verily employee leaked.

Roche is also making progress in its Diabetes Care Unit. It has struck a deal with the MedTech company Senseonics to sell an implantable glucose sensor in some major European countries.

With an app, patients then can access real-time glucose measurements. The software also predicts the ‘wobble’ in glucose levels, so that patients can take steps to stay in control if they are near to developing a hypo or hyperglycemic episode.

glucose_monitoring_polymer_fluorescent_senseonics

Implanted under the skin in the arm, the sensor antenna receives radiofrequency energy from a smart transmitter (left) and the indicator polymer on the sensor’s surface fluoresces when glucose temporarily binds to it (Source: Senseonics)

A Monitoring-Delivery Combo?

Automated pancreatic simulation is an interesting alternative to the standard insulin injections, as these might not always best match the rapid changes in blood glucose throughout the day. In addition to an intradermal pump, Cellnovo’s mobile system comprises a handset from which the patient can control the pump.

A research team from the University of Cambridge has also managed to develop a closed loop beta-cell based insulin delivery system for diabetes type I. This bionic pancreas prototype has been constructed for human trials using an iPhone app which monitors blood glucose levels.

bionic_pancreas_ilet_boston_cyborg_biotech_medtech_diabetes_review

The iLet by the Boston Group (Source: Bionic Pancreas Project) and a generic model of the components to a bionic pancreas (Source: Barabara Davis Center)

A similar research development has been made by Boston’s Bionic Pancreas project, which completed its 22-day outpatient trial in April of last year. In collaboration with Boston University and Massachusetts General Hospital, the Bionic pancreas has been branded the iLet.

However, this kind of system has been scrutinised by the ‘Biohacking’ community and even parents – particularly in the States, where this kind of MedTech could potentially be too far-off from regulatory approval or too costly for some patients.


But is Cell Therapy the Ultimate Cure?

Bolstering up dysfunctional tissue with transplant tissue to enhance insulin production is also a popular area of development.

The Diabetes Cell Therapy Institute (DCTI) is a research initiative looking to improve pancreatic beta-cell replacement therapy (Islet transplantation) as well as helping improve patient accessibility to such therapies.

Along with other attempts to create islets in the lab (and bypass the problem of donor shortage), these procedures seem to be the future of treatments for type 1 diabetes. On this front, the DCTI is even partnered up with some biotechs, including the well-known Galapagos.

islet_cell_transplant_type1_diabetes_research

Traditional procedure for islet cell transplant. (Source: Diabetes Research Institute).

Islet transplants have actually already been around for a while though. In 2000, patients in a trial were able to stop their daily insulin injections after successful transplants – which sounds like the end of diabetes altogether!

But not so fast. The problem was, that although transplantation does technically work, donor islets tend to fail in insulin production over time, which is why the DCTI is looking to optimise pancreatic islet isolation from donors. Therefore, different surgical and transplant methods have been investigated to improve islet transplantation.

Here the DCTI in Groningen (Netherlands) explains the Islet Transplant problem…

Which brings me to news we just covered yesterday – a new surgical method using part of the stomach cell lining has resulted in the successful ‘cure’ of a patient at a hospital in Milan. This is the first example of successful proof-of-concept of this kind of Islet transplant technology in Europe, which was developed at the Diabetes Research Institute (DRI) at the University of Miami.


So is this the end?

So there we have 3 broad areas in which diabetes is being tackled in biotech: new analogues for insulin and insulin-stimulating hormones, improved delivery and monitoring of existing therapies, and lastly, cell therapy.

It is by no means an exhaustive list of all those working in diabetes but will hopefully bring together some of the angles used by the field to approach the disease. Considering that some of these trials are reaping dramatic results, it’s encouraging to keep the scale of how much has been already accomplished in mind.

However, there is much left to still work out, and with patents expiring and many trials still in early stages, it would be overly optimistic to say we’ve made it just yet.


Feature Image Credit: Pancreas and spleen -© Krishnacreations (BioStock ID54709022)
Fig. 1 Owens (2002) New horizons — alternative routes for insulin therapyNature Reviews Drug Discovery, 1, 529-540, doi:10.1038/nrd836

Update 17/06/2016: we added mentions to Humulin, made it clearer on delivery issues, Intarcia’s clinical trials, 

ADVERTISEMENT
Previous post

British Biotech startup shows 50% improvement in Atopic Dermatitis

Next post

Dutch Fund raises €250M to invest in Late Stage Biotechs

  • Carlos Azuaje

    Good to see the problem being tackled from different angles.

    The work being done by the DCTI consortium is very encouraging also!

    Nice review, Dani 😉

  • Dave Y

    Good overview, yeah there’s a number more you could have highlighted.

    • Thanks, Dave. I agree. Perhaps we will explore more in a future review to cover those I haven’t.

  • satyanaryana raju

    It is by no means an exhaustive list of all those working in diabetes but will hopefully bring together some of the angles used by the field to approach the disease. Considering that some of these trials are reaping dramatic results, it’s encouraging to keep the scale of how much has been already accomplished in mind.