The first glucagon analogue: the first stage of the trial of severe hypoglycemia

The first glucagon analogue: the first stage of the trial of severe hypoglycemia

September 20, 2018 Source: Sina Pharmaceutical News

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On September 18th, the Dutch pharmaceutical company Zealand Pharma, which specializes in the development of peptide drugs, announced that its drug candidate dasiglucagon for critical hypoglycemia treatment in critical clinical phase 3 trials reached the main study endpoint and key secondary study endpoints.

This key phase 3 trial showed that a single dose of dasiglucagon can rapidly increase blood glucose levels in patients with type 1 diabetes caused by an absolute deficiency in insulin. The trial compared blood glucose responses in patients taking dasiglucagon, placebo, and currently marketed glucagon drugs. The primary endpoint of the study was the time to recovery of blood glucose levels in the blood, ie, the first increase in blood glucose from baseline at 20 mg/dl (1.1 mmol/l) without first-in-time glucose infusion. A total of 168 subjects participated in the trial: 82 were assigned to the dasiglucagon group, 43 to the placebo group, and 43 to the glucagon treatment group.

Preliminary results showed that the median time to glycemic recovery was 10 min in the dasiglucagon group, which was superior to the placebo group (median 40 min; p<0.001), while the median time to recovery in the glucagon group was 12 min. 99% of subjects recovered from insulin-induced hypoglycemia within 15 minutes of taking dasiglucagon, compared with 2% and 95% for placebo and glucagon, respectively.

In general, dasiglucagon did not cause any safety problems during the test. Dasiglucagon and glucagon have been reported to have similar nausea and vomiting in patients (nausea: 55% and 53%, vomiting: 23% and 19%).

This is the second clinical trial of dasiglucagon with positive results. The last phase 3 trial confirmed the safety of the drug. The company will begin a clinical phase 3 trial of children with diabetes and is expected to be completed by mid-2019.

Dasiglucagon is a soluble glucagon analog found and developed by Zealand that has the world's first-in-class potential. The drug has unique stability in liquid preparations, and the clinical treatment is convenient, rapid and effective in the treatment of severe hypoglycemia in the form of a HypoPal rescue pen. Other indications under development include: treatment of type 1 diabetes for a new generation of artificial pancreas; children with congenital hyperinsulinemia (CHI) due to genetic mutations.

Severe hypoglycemia is an acute, life-threatening condition that is primarily associated with a severe decline in blood glucose levels associated with insulin therapy, most commonly in patients with type 1 diabetes caused by daily insulin injections. The disease is the most concerned issue for insulin-dependent patients and the most horrible complication of diabetes treatment. The disease is characterized by mental confusion, seizures, and, if left untreated, often leads to death. When a patient has a hypoglycemic event, a second person is required to assist with the treatment. Glucagon preparations currently marketed for the treatment of severe hypoglycemia need to be first mixed by a person who is assisted in the treatment, and then must be administered immediately due to poor drug stability. Dasiglucagon may be a ready-to-use stable formulation for rescue treatment.

Adam Steensberg, chief pharmaceutical development officer at Zealand Pharmaceuticals, said: "I believe the results of the Phase 3 trial are excellent and show that the dasiglucagon HypoPal can be the best choice for treating severe hypoglycemia. Thanks to the patients and clinical researchers involved in the trial. ."

Thomas R. Pieber of the Department of Endocrinology and Diabetes at the Medical University of Graz said: "The results of this phase 3 trial are impressive because all patients have a corresponding clinical increase in blood glucose levels within 15 minutes, with a median recovery time only It is 10 minutes. For diabetic patients with severe hypoglycemia, dasiglucagon may become a very attractive treatment."

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