There’s 11 days left in 2019, but what did Breakthrough T1D see this year that said “breakthrough”? This top 10 list reflects advances in type 1 diabetes (T1D) research, with many funded by Breakthrough T1D or the Breakthrough T1D T1D Fund. Other type 1 diabetes research breakthroughs in 2019 were advanced by the National Institutes of Health’s Special Diabetes Program, The Leona M. and Harry B. Helmsley Charitable Trust, or by the private sector that made T1D a priority in their research and development programs.
Here are the top 10 type 1 diabetes research breakthroughs that Breakthrough T1D is proud of:
1. The second artificial pancreas system approved by the FDA
In December, the Food and Drug Administration (FDA) authorized an algorithm that enables the second artificial pancreas system: the Tandem Control-IQ™ advanced hybrid closed loop technology. It’s the first algorithm authorized as an interoperable automated glycemic controller, which means the algorithm could be a component of any open protocol, or interoperable, artificial pancreas system (for now, though, the algorithm can be used with Tandem’s t:slim X2™ insulin pump and Dexcom’s G6 continuous glucose monitor (CGM)). Data came from the International Diabetes Closed Loop Protocol-3 (iDCL) trial, funded by the Special Diabetes Program. The study met all of its primary and secondary endpoints, including time-in-range and HbA1c, with no fingerpricks and no severe low blood sugar events—a dangerous event for people with T1D.
Breakthrough T1D has been a leader in artificial pancreas systems for 15 years, from developing a roadmap for artificial pancreas development and partnering with the FDA and the Helmsley Charitable Trust to create a regulatory pathway for approval and commercialization of this technology. Industry experts have said that Breakthrough T1D’s involvement cut five years off the approval process for the Medtronic 670G artificial pancreas system in 2016, the first approved system.
This is a win for the T1D community, and provides people with T1D another option to improve daily blood-sugar management.
2. Teplizumab delays T1D for more than 2 years
For the first time ever, an immune therapy treatment, called teplizumab, was able to significantly delay—for over two years—the onset of T1D in participants with a high risk of developing the disease. Breakthrough T1D funded one of the first clinical trials of this drug, and funds TrialNet, who conducted the study. Teplizumab is now being tested in a phase III clinical trial in people recently diagnosed with T1D, headed by Provention Bio, a company with an investment from the Breakthrough T1D T1D Fund. The FDA has also granted Breakthrough Therapy Designation to teplizumab in individuals at-risk of developing the disease.
3. European approval of two adjunct therapies
The European Commission has approved two medications that help in glucose management by preventing the kidneys from reabsorbing glucose back into the blood. The Commission approved SGLT inhibitors for T1D: Forxiga® (dapagliflozin and marketed in the United States as Farxiga) and Zynquista™ (sotagliflozin), when used in conjunction with insulin to improve glycemic control.
4. FDA approves two treatments for low blood sugar
The FDA approved Baqsimi, the first non-injectable emergency treatment for severe episodes of low blood sugar (hypoglycemia). Severe hypoglycemia means that another person has to administer treatment because the person with T1D has impaired or lost consciousness or may be having a seizure. Injectable glucagon has been approved in the United States for several decades, but this is the first non-injectable treatment. The FDA also recently approved a glucagon pre-filled syringe and auto-injector created by Xeris Pharmaceuticals, which is also funded by Breakthrough T1D to develop a bi-hormonal pump with insulin and glucagon. The GVOKE line of products features the first pre-mixed, pre-filled liquid glucagon formulation on the market.
5. Pharma makes a landmark investment in T1D research
In the largest deal to date of a T1D cure-based therapeutic program, Vertex Pharmaceuticals acquired Semma Therapeutics for $950 million. Semma was founded in 2015 with the goal of commercializing research to make beta cells from human-derived stem cells. The research team, led by Douglas Melton, Ph.D., had support from Breakthrough T1D since 2000 and, in 2017, the Breakthrough T1D T1D Fund provided an important investment in the company.
6. Recommendation: Pregnant women with T1D use continuous glucose monitors (CGMs) to monitor blood sugar
The United States has joined Australia and the United Kingdom in recommending that CGMs be used to improve HbA1c outcomes in pregnant women with T1D. Breakthrough T1D funded the CONCEPTT trial, which showed that using a CGM during and prior to pregnancy improves the health outcomes for both mothers and babies. It was the CONCEPTT trial that made the American Diabetes Association revise its clinical guidelines.
7. Clinical trial results: TTP399 was able to reduce HbA1c by 0.7%
A protein, called glucokinase (or GK), acts as a key regulator of sugar levels in the body. If blood glucose levels are deemed too high, activation of GK in the liver causes the body to use more glucose, which in turn lowers glucose levels in the blood. vTv Therapeutics has developed a GK activator, called TTP399, and joined forces with Breakthrough T1D in 2017, to test it in people with T1D. In a clinical trial, the TTP399 group had a significant and clinically meaningful reduction of 0.6% in their HbA1c, whereas those in the placebo group increased their HbA1c by 0.1%. These promising findings support advancing to phase II-part 2 to confirm the results in a larger and more diverse T1D population.
8. End-stage kidney disease: A possible therapeutic target for people with T1D
In the United States, diabetic kidney disease is responsible for more than half of all new cases of end-stage kidney disease. Breakthrough T1D-funded researchers Monika Niewczas, M.D., Ph.D., M.P.H., and Andrzej S. Krolewski, M.D., Ph.D., however, found 17 inflammatory proteins that were strongly associated with progression for end-stage kidney disease. This adds 15 such biomarkers to the two they identified in 2012. Many of the proteins are currently being tested in clinical trials for other chronic inflammatory disorders. Further testing these compounds in diabetic kidney disease may offer hope to people living with T1D that they may thwart end-stage kidney disease altogether.
9. Better insulin-producing beta cells from stem cells
Breakthrough T1D-funded researchers have introduced an inventive step in the process of making mature insulin-producing beta cells from stem cells, with the resulting cells responding to blood sugar more like human beta cells. What’s more, after transplantation, these beta cells were functional in a matter of days. (Research thus far has insulin-producing beta cells responding to blood sugar challenges only 2 to 6 weeks after transplantation.) Not only does their discovery set the stage for cell therapy, since they can now make human beta cells in a dish, it opens avenues for finding novel drugs that can stimulate the expansion of beta cells.
10. Collaboration with cancer researchers
A subset of people with cancer who receive checkpoint inhibitor therapy, which is used to “release the brakes” on the immune system, go on to develop T1D or other autoimmune diseases. We want to know why. In 2019, Breakthrough T1D and The Leona M. and Harry B. Helmsley Charitable Trust teamed up with the Parker Institute for Cancer Immunotherapy to uncover the mechanisms of how autoimmunity develops in these people. We will follow 1,600 people with cancer who receive checkpoint inhibitor therapy, and who subsequently develop autoimmune diabetes—with the ultimate goal to develop therapies to prevent or treat this disease.
What type 1 diabetes research breakthroughs will 2020 bring?
