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. So let’s have a look at what innovative therapies biotech is working on to fight it.
Cell therapy: is a cure possible?
The Diabetes Research Institute (DRI) in the US is bidding for a form of therapy that could cure diabetes. Indeed, the first patient has effectively been cured in an ongoing Phase I/II trial, and she no longer requires insulin therapy. Such a miraculous treatment is the DRI BioHub, an engineered mini-organ that behaves like a native pancreas.
“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,” stated Camillo Ricordi, Director of the DRI in a press release.
On top of that, 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. And with a whole different approach, NeoVacs, in France, is developing a diabetes vaccine that could stop the progression the disease.
However, these technologies are still far from the market. Some are actually skeptical about their success, since such a therapy might not be suitable for many people due to safety risks. In addition, the cost could end up being astronomical, which could be difficult to justify for a disease that’s not immediately life-threatening. Insurers might be reluctant to cover the massive price of a cell therapy upfront instead of a lifelong treatment as is common today. So, 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, told Medgadget. And that world is not so far way. Many are awaiting the arrival of noninvasive alternatives for glucose monitoring, which currently requires the use of needles multiple times a day.
The days of pricking fingers to test blood sugar are counted thanks to companies like Israeli Integrity Applications, whose device GlucoTrack can measure glucose using electromagnetic waves and is already available in Europe.
MediWise, in London, is developing GlucoWise, a portable device that could outperform all competitors by measuring glucose using radio waves. As co-founder Panos Kosmas told us in an interview, he expects to launch the device two years from now.”The device could reduce costs for healthcare, which in the case of diabetes account for €90Bn a year in Europe.”
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.
Automatic care for type 1 diabetes
As Roman Hovorka, Professor at the University of Cambridge, explained to me during an interview, “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.”
Still, patients are currently required to self-administer what they consider the best insulin dose daily. But Hovorka himself is working on an artificial pancreas: a medical device that can measure glucose levels and automatically deliver the right amount of insulin. His team is working on a fully automated algorithm that could be available within the next 5 years.
While we wait for it, other medtech companies are launching their own automated insulin pumps. Medtronic recently received FDA approval for such a device, although it still requires manual input after every meal.
Another player in the field is CellNovo, which sells a pump that can be controlled wirelessly through a mobile app. The French company is also investing in developing an artificial pancreas in the coming 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,” stated Kurt Graves, President and CEO of Intarcia, in a press release.
Biotech seems determined to put an end to this, and it looks like the next big thing for first-line treatments in diabetes type 2 are glucagon-like peptide (GLP)-1 receptor agonists. These molecules can induce insulin production in beta-pancreatic cells while suppressing glucagon secretion, and all big pharma have GLP-1 drugs on the market or their pipelines, including Sanofi, Novo Nordisk, Eli Lilly, Roche, AstraZeneca and Boehringer Ingelheim.
The unicorn Intarcia is going one step further. The company recently 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.
The Quest for the Best Insulin
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 currently a crisis with rising insulin prices and biosimilars are starting to enter the scene. For example, Eli Lilly’s Abasaglar, a biosimilar of Lantus, could bring a reduction of the price of Sanofi’s drug by 20%.
“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.
And indeed, 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 thanks to a partnership with Sanofi to explore insulin delivery using its TransCon technology, which could reduce dosing up to every 6 months.
With the rapid increase in prevalence, the already crowded diabetes market is expected to reach an massively big €86Bn by 2025 combining both type 1 (€32Bn) and type 2 (€54Bn) 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,” said Tomas Landh, Director of Strategy and Innovation Sourcing at Novo Nordisk, 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.
Featured image by MihaStock/shutterstock.com; images from MMediWise; Hui Won Yun, Seoul National University; Medtronic; Intarcia; A. N. Zaykov et al., Nature Reviews Drug Discovery 15,425–439