Dasiglucagon for use in a pump setting

Dasiglucagon is a glucagon analog invented and fully owned by Zealand. It has a favorable stability profile in a liquid formulation and is a potential first-in-class glucagon analog suitable for pump use. This may provide diabetes mellitus patients treated with insulin an option for more effective, safe and easy diabetes management.

Type 1 diabetes

People with type 1 diabetes suffers from insulin deficiency and inappropriate glucagon secretion. Both hormones are essential to ensure stable and healthy blood glucose levels. Patients must monitor and adjust their blood sugar levels to remain in proper glycemic control, as both high and low blood glucose may affect their health, both in the short and long term.

As glucagon is not yet available in a liquid formulation, no pump systems capable of mimicking a healthy pancreas are available today. Dasiglucagon has the potential to be the first glucagon analog for chronic use in a future dual-hormone artificial pancreas. Globally, more than 20 million people have type 1 diabetes (IDF) and are facing challenges in managing hypoglycemia and achieving good glycemic control.

*Dasiglucagon is a proposed International Nonproprietary Name (pINN).
*The iLET from Beta Bionics

Phase 2a trial results support development of dasiglucagon in the iLet™ pump system

The aim of the Phase 2a clinical trial was to assess the safety, efficacy and tolerability of dasiglucagon when administred automatically using the iLet™ algorithms. The trial included 10 adult patients with type 1 diabetes, and a marketed recombinant glucagon was used as comparator. The test conditions were chosen to optimize the opportunity to evaluate the ability of dasiglucagon (and comparator) to maintain blood glucose in the desired target glycemic range: subjects arrived fasting at the clinic for the 8 hour testing period, they had their first meal at lunch-time at which time they injected a standard insulin bolus. Their basal rate of insulin was up to twice their normal rate, and following the meal, they were asked to perform 30 minutes of exercise to stimulate the administration of glucagon by the system.

 Collaboration with Beta Bionics

In 2016, Zealand and Beta Bionics, a medical technology company, entered into a collaboration, the objective of which is to combine product rights from each party to advance a new dual-hormonal artificial, or bionic, pancreas system. Such a system has the potential to offer people with diabetes on insulin therapy more efficacious, safer and easier blood sugar control for better long-term disease management and outcomes.

The system under the collaboration is based on an advanced bionic pancreas platform technology, developed at Boston University, which has been integrated into a pocket-sized wearable medical device, called the iLet™. Boston University has granted an exclusive worldwide license of the iLet™ technology to Beta Bionics. The bionic pancreas technology in the iLet™ is designed for automated delivery of both insulin and glucagon and has been tested and refined for nearly 10 years in clinical trials.

Hypoglycemia and dual-hormone bionic pancreas

Hypoglycemia is a condition in which blood glucose drops to unsafe levels. It is most frequently associated with diabetes and primarily arises in people with type 1 diabetes and those with type 2 diabetes who are on insulin therapy. According to Decision Resources, all people with type 1 diabetes and approximately 20% of people with type 2 diabetes in the United States are treated with insulin. People with 1 diabetes are the most likely to experience episodes of hypoglycemia since they often inject themselves with insulin up to six times per day or use an insulin pump.

Symptoms of a hypoglycemic episode include anxiety, sweating, tremors, palpitations, nausea, and pallor. In severe cases, hypoglycemia can lead to loss of consciousness, seizures, coma, and death. Severe hypoglycemia or “insulin shock” occurs when blood glucose levels become so low that the assistance of another person is required to treat the condition, which typically involves administration of intravenous glucose or glucagon injection. Severe hypoglycemia is classed as a diabetic emergency. According to the American Diabetes Association, hypoglycemia occurs frequently and the fear of another episode often leads to conservative insulin administration and poor glucose control (i.e., allowing blood glucose to remain higher than desired), which, in turn, increases risk of micro- and macrovascular complications (Diabetes Care. 2013, 36:1384–95).

It is also clear that people with type 1 diabetes who experience frequent hypoglycemia become unaware of the symptoms and are then predisposed to most severe expression of the condition because they do not feel the more, subtle impending signs. Many people with type 1 diabetes have hypoglycemia for several hours overnight, which, in itself, is dangerous, but which can also lead to hypoglycemic unawareness in the daytime. (Acta Diabetologica. 1998, 35:183–93) Furthermore, hypoglycemia is considered especially unsafe for children with type 1 diabetes under the age 6, who’s developing brains can be adversely affected by low blood sugars at a level which might not cause harm for the more mature brain. (Journal of Pediatrics. 1999, 134:492–98).