Glucagon for the dual hormone artificial pancreas
Lisa Foster-McNulty, MSN, RN, CDE
The alpha cells of the pancreas produce glucagon, and it is secreted to prevent blood glucose levels from dropping too low. A peptide hormone, glucagon plays an essential role in a well-functioning metabolic system. It’s difficult to use glucagon therapeutically because it has poor solubility and low stability in liquid solution. If you know Type 1 diabetes, you know that glucagon is reconstituted just prior to use.
A company called Zealand has invented an analog of human glucagon. It has a proposed International Nonproprietary Name (pINN) of Dasiglucagon. It has been shown to have high solubility and strong physical and chemical stability in liquid solution. Information from preclinical studies indicates that this product is comparable to native glucagon in its ability to release glucose stores into the blood stream. In rat studies, after using insulin to induce hypoglycemia, dasiglucagon was able to quickly and in a dose-dependent fashion restore blood glucose to baseline levels or greater. This novel analog has demonstrated an effect on blood glucose that is similar to native glucagon in dogs, and it is metabolized from the body in a similar manner.
In collaboration with Beta Bionics, Zealand is working to develop a first-in-class dual-hormone artificial pancreas system to treat Type 1 diabetes. The goal of this collaboration is to combine the necessary proprietary product rights from each party to bring a dual-hormone artificial pancreas system to the next phase of its clinical development. Such a product has great potential to give people with diabetes who use insulin a safer, easier, and more effective method of controlling diabetes, and can lead to better health outcomes. The new system, developed at Boston University and Beta Bionics, is integrated into a wearable medical device, the iLet. Boston University has given Beta Bionics an exclusive worldwide license of the iLet technology. The bionic pancreas technology in the iLet automates delivery of both insulin and glucagon analogs. It has been tested and fine-tuned in close to 10 years of clinical trials. These trials utilized recombinant human glucagon, which had to be reconstituted on a daily basis.
Concluded in September of 2015, a Phase Ib clinical trial with Dasiglucagon provided data to support that Dasiglucagon was safe and well-tolerated, and provides a clinically relevant blood glucose response following repeat daily dosing in healthy volunteers. Study results supported the use of a multiple-dose version, including potential to be used in an artificial pancreas system, to correct low blood glucose levels in patients with Type 1 diabetes. The primary goal of this randomized, placebo-controlled, double-blind trial was to investigate the tolerability and safety of Dasiglucagon after multiple dosing.
In December of 2016, Zealand started two Phase IIa trials using Dasiglucagon. These trials are the foundation for longer clinical trials with a multiple-dose version of Dasiglucagon in the dual-hormone artificial pancreas system.
The goal of the first Phase IIa clinical trial with Beta Bionics is to look at the safety, effectiveness, and tolerability of Dasiglucagon as part of the Beta Bionics dual-hormone artificial pancreas system in adults with Type 1 diabetes, compared to a recombinant market glucagon. As for the second Phase IIa trial, its purpose is to evaluate the pharmacokinetic (“what the body does to the drug”) and pharmacodynamic (“what the drug does to the body”) responses after the multiple-dose version of Dasiglucagon is given to adult patients with Type 1 diabetes. The first patients in this trial have already been dosed.
Progress is being made!
The goal is to have a commercially available “bionic pancreas” product that uses insulin as well as glucagon, automating delivery of these hormones so that people with diabetes who use insulin have an easier, safer, and more effective way of managing this disease to achieve better health outcomes. Slowly but surely, we’re getting there.