JDRF, a global organization funding type 1 diabetes (T1D) research, has partnered with both Xeris Pharmaceuticals and Latitude Pharmaceuticals (LPI) to support the development soluble glucagon formulations—a step toward the advancement of future-generation, fully automated and multi-hormonal artificial pancreas systems for people with (T1D).
First-generation artificial pancreas systems currently being tested in JDRF-supported outpatient clinical trials use technologies already available; they combine a continuous glucose monitor (CGM) with an insulin pump using computer software to partially automate the right amount of insulin delivery for people with T1D.
"Studies have demonstrated the game-changing value of first generation artificial pancreas systems in improving blood-glucose control and alleviating some of the burdens of managing type 1 diabetes," said Sanjoy Dutta, Ph.D., JDRF's senior director of treat therapies. "Still, future-generation artificial pancreas systems are expected to do even more. To become fully automated, closed loop systems, new technologies and drugs—including stable, pumpable glucagon—will be required in order to more closely and accurately mimic the functions of a healthy pancreas. Both near-term and long-term projects to advance the artificial pancreas are important research priorities for JDRF."
While first-generation artificial pancreas systems will deliver insulin, one of the aspects of future generations will be their ability to deliver multiple hormones, such as glucagon. Glucagon is a naturally occurring hormone that raises blood-sugar levels to prevent hypoglycemia (low blood sugar), but its regulation is impaired in people with T1D. In a healthy pancreas, it complements the function of insulin to provide the natural fine-tuning of blood-glucose control, and previous studies supported by JDRF and others have shown that the addition of glucagon to insulin treatment in T1D reduces the frequency of hypoglycemia.
One hurdle in developing an advanced-generation, multi-hormonal artificial pancreas system is that commercially available glucagon does not remain stable; the powder and solution mix into a short-lived liquid form not suitable for long-term use in a pump. Xeris and LPI will develop two different approaches to making glucagon usable for infusion pumps.
Xeris—a specialty pharmaceutical company based in Austin, Texas, focused on developing injectable therapeutics—will study its stable, room-temperature and non-aqueous injectable glucagon (G-Pump Glucagon) to treat hypoglycemia. Clinical studies will take place at Oregon Health & Science University (OHSU) with two years of milestone-based funding from JDRF.
"Our partnership with JDRF enables us to move forward in pursuing an improved approach to controlling blood glucose levels by enabling a fully closed-loop system that addresses both hyperglycemia and hypoglycemia," said Steve Prestrelski, Ph.D., chief executive officer at Xeris.
LPI—a San Diego-based drug formulation development company—will use a unique, proprietary, solvent-free, glucagon nanoemulsion (Nano-G) to solubilize and stabilize the molecule, such that it is not vulnerable to degradation and remains biologically active. With milestone-based funding from JDRF for one year, LPI plans to begin clinical testing in the U.S. in 2014.
"This partnership will accelerate Latitude’s stable, soluble glucagon formulation and its potential for new medical applications,” said Andrew Chen, Ph.D., LPI's president. “Our partnership with JDRF will give us an opportunity to provide a missing piece needed to make the bi-hormonal artificial pancreas a reality."