Another interesting artical. It's as if Mannkind doesn't exist !
labiotech.eu/diabetes-review-insulin-glp-needle-free/With 422 million people suffering from diabetes, the disease has become an epidemic. There’s still no cure and medicine is struggling to provide an efficient solution. However, from needle-free glucose monitoring to an artificial pancreas, biotech is working on it.
Diabetes is a chronic disease that affects the regulation of insulin, a hormone required for glucose uptake in cells. While type 1 is an autoimmune disease that destroys the insulin-producing beta-pancreatic cells, in type 2 these cells still function but the body develops insulin resistance as a consequence of obesity, highly caloric diets and lack of exercise.
The number of people with diabetes, the major cause of blindness, kidney failure, heart attack and stroke, has risen from 108 million in 1980 to 422 million in 2014. The World Health Organization (WHO) considers it an epidemic and predicts it will become the 7th biggest cause of death worldwide by 2030.
Earlier this year we reviewed some of the progress science has made to help diabetic people. But there’s plenty more happening in this incredibly crowded field.
Cell Therapy: is a Cure possible?
This can be the beginning of a new era in islet transplantation. Our ultimate goal is to prevent the need for life-long anti-rejection therapy.” Camillo Ricordi, Director of the Diabetes Research Institute (DRI) in the US, stated in a press release
The first patient has effectively been cured and she no longer requires insulin therapy. The Phase I/II trial is testing the DRI BioHub, an engineered mini-organ that behaves like a native pancreas.
Other companies, like the British Catapult and the Belgian Orgenesis are using a different approach and grow the patient’s own pancreatic cells in the lab. Out in the US, ViaCyte and Semma Therapeutics are working in differentiating stem cells into beta cells that can produce insulin normally.
MaSTherCell
Orgenesis’ MaSTherCell stem cell therapy manufacturing facilities
However, the technology is still far from the market. Some are actually skeptical about its success since the therapy might not be suitable for many people due to safety risks. In addition, a source within the diabetes industry told us:
Unlike cancer, diabetes is not a life-threatening disease and therefore there’s no justification for the high price that a cell therapy would have.”
With a whole different approach, NeoVacs, in France, is developing a diabetes vaccine that could stop the progression the disease. But since a cure might not be feasible at the moment, what is everyone else doing to treat the disease?
The Needle-Free Revolution
In a perfect world, blood sugar testing would be quick and painless.” Avner Gal, CEO of Integrity Applications, for Medgadget
Many are awaiting the arrival of non-invasive alternatives for glucose monitoring, which currently requires the use of needles multiple times a day. Now, the days of pricking your fingers are counted: Integrity Applications’ GlucoTrack, from Israel, can measure glucose using electromagnetic waves and is already available in Europe.
MediWise, in London, is developing GlucoWise, a portable device that measures glucose using radio waves and could outperform all competitors. One of the co-founders told us in an interview:
We estimate we can launch the device two years from now. The device could reduce costs for healthcare, which in the case of diabetes account for €90B a year in Europe.”
GlucoWise diabetes sensor
The GlucoWise sensor
GlucoSense, also in London, is developing a similar device that uses laser light instead. Other companies are exploring a different approach and measure glucose indirectly in the eye’s tear fluid instead: NovioSense via an implant and Google with a smart lens.
Other less invasive alternatives in the works include FreeStyle Libre, from Abbott Diabetes Care in the UK, an inch-wide patch that can be worn for up to 2 weeks. There’s also Eversense, a subcutaneous implant that measures glucose in interstitial fluids and lasts up to 90 days. Roche recently struck a deal with the developer, Senseonics, to distribute the sensor.
Graphene patch for diabetes tytpe 2
A team from the Seoul National University is developing this futuristic graphene patch, which can sense glucose in sweat and release metformin in patients with diabetes type 2
Automatic Care for Diabetes Type 1
Diabetes type 1 is very different from your standard disease. Insulin requirements vary greatly from one day to another and there is no way patients can know what they need.” Roman Hovorka, from University of Cambridge, told us
Medtronic MiniMed 670G for diabetes type 1
Medtronic MiniMed 670G
Accounting for up to 10% of all cases of diabetes, people diagnosed with diabetes type 1 need daily insulin injections. MedTech seems to be the main trend to deal with such a burden, with amazing examples like CellNovo‘s mobile app to control insulin pumps.
The long-awaited solution might be relying on computer algorithms to take decisions for us: the artificial pancreas is a medical device that can measure glucose levels and automatically deliver the right amount of insulin. Medtronic recently received FDA approval for such a device, although it still requires manual input after every meal.
A better version is already on track: Cambridge is working on a fully automated algorithm that could be available within the next 5 years.
Type 2: Everyone is after GLP-1
During the past decade over 40 new pills and injections were approved for diabetes. However, the scary reality is that the majority of patients with type 2 diabetes still have poor glycemic control.” Kurt Graves, President and CEO of Intarcia, stated in a press release
It looks like the next big thing for first-line treatments in diabetes type 2 are glucagon-like peptide (GLP)-1 receptor agonists, which induce insulin production in beta-pancreatic cells while suppressing glucagon secretion. All big pharma have GLP-1 drugs on the market or their pipelines: Sanofi, Eli Lilly, Roche, AstraZeneca…
Intarcia medici pump for diabetes type 2
Intarcia’s medici pump
The unicorn Intarcia will bolster their efforts. The company just filed for FDA approval for a GLP-1 osmotic mini-pump that is implanted once or twice a year instead of the usual daily or weekly injections.
Meanwhile, Novo Nordisk is working on semaglutide, an oral GLP-1 that would get rid of injections at all, currently in Phase III. Unfortunately, the company had to drop its oral insulin recently due to market pressure, which brings us to…
The Quest for the Best Insulin
It’s getting crowded, and in order to differentiate it’s not just sufficient any longer to have the best insulin. You have to go beyond that.” Stefan Oelrich, Head of Sanofi’s Diabetes Franchise, told Bloomberg
The high insulin demand helped Sanofi’s Lantus (insulin glargine) and Novo Nordisk’s NovoRapid (insulin aspart) make it to the top 10 best-selling biologicals. However, there’s a crisis with rising insulin prices and biosimilars are entering the scene: Eli Lilly’s Abasaglar could reduce the price of Lantus by 20%.
Insulin modifications for diabetes
Insulin structure (a) and sequence modifications approved for diabetes treatments (b)
While big pharma fight the price war, an ultra-fast-acting insulin is under development to address the slow absorption time of this essential drug. Eli Lilly’s BioChaperone Lispro, developed in partnership with the French Adocia and currently in Phase III, could reduce the absorption time from 60 to 42 min. Us-based Biodel is working in BIOD-123, an insulin analog that could reduce the time to around 20 min and has completed Phase II.
Others are searching for the opposite: an ultra-long-acting insulin that can reduce the frequency of injections, which currently is at 1 or 2 per day. Novo Nordisk, PhaseBio, AntriaBio and Hanmi Pharmaceutical are all working on versions that can be delivered once a week. However, Ascendis Pharma, in Denmark, might outperform them all: it partnered with Sanofi to explore insulin delivery using its TransCon technology, which can reduce dosing up to every 6 months.
What’s Next?
With the rapid increase in prevalence, the already crowded diabetes market is expected to reach an impossibly big €86B by 2025 combining both type 1 (€32B) and type 2 (€54B) treatments. With such a big space for competition, revolutionary technologies will surely arise.
Researchers are already speculating about microchips that can diagnose diabetes type 1 before the symptoms appear or nanorobots traveling in the bloodstream while they measure glucose and deliver insulin.
There’s little fiction left in this. I strongly believe that microrobotics will come and will be part of our drug delivery within the next 10 years perhaps.” Tomas Landh, Director of Strategy and Innovation Sourcing at Novo Nordisk, said at the 2013 Medicon Valley Alliance Annual Meeting
Whatever the future brings, it will undoubtedly make a huge difference in the lives of millions of people worldwide.
Nanorobots vs diabetes
Will the future bring nanorobots fighting against diabetes?
Featured image by MihaStock/shutterstock.com; images from MaSTherCell; MediWise; Hui Won Yun, Seoul National University; Medtronic; Intarcia; A. N. Zaykov et al., Nature Reviews Drug Discovery 15,425–439 (2016); Ktsdesign/shutterstock.com
