Xeris Pharmaceuticals, Inc., a speciality pharmaceutical company using its novel formulation technology platforms to develop and commercialize ready-to-use injectable and infusible drug formulations, announced that the European Commission (EC) Ogluo  (Glucagon ) as an injection for the treatment of severe hypoglycaemia in adults, adolescents and children 2 years and older with diabetes mellitus. The approval is valid in all 27 countries of the European Union as well as in Iceland, Norway and Liechtenstein. Since the commission decision was received after the end of the Brexit transition period, Xeris will go through another administrative step to obtain approval in the UK.

“This EU approval for Ogluo is an important milestone for Xeris and a significant advancement in the treatment of severe hypoglycemia for the diabetes community in Europe. Hypoglycemia is the # 1 side effect of insulin, and severe hypoglycemia is the most acute emergency a person with diabetes can experience. Ogluo, the first premixed auto-injector for severe hypoglycemia, can help offset the risk associated with insulin, ”said Paul R. Edick, chairman and chief executive officer of Xeris Pharmaceuticals. "We are preparing to bring Ogluo to market later this year while we are also looking for a marketing partner to expand Ogluo's availability to other European countries."

The European Commission's approval was supported by data from a multicenter, randomized, control group, non-inferiority phase 3 study. The study was conducted among 132 adults in Europe and North America with type 1 diabetes to use the liquid and stable glucagon auto-injector as a treatment for severe hypoglycemic events versus the GlucaGen  -HypoKit from Novo Nordisk to evaluate. The results showed comparable effectiveness between the two groups in terms of achieving a plasma glucose level of more than 3.89 mmol / L (> 70 mg / dL) or a relative increase in plasma glucose concentration of 1.11 mmol / L (≥20 mg / dL ) within 30 minutes of administration. The study also found that the time it took for symptoms of hypoglycemia to subside and the time for the general impression of hypoglycemia to subside were comparable. No concerns regarding safety or tolerability were identified. The most common adverse effects in this study were nausea and vomiting.

“Hypoglycaemia is an often neglected complication of glucose-lowering therapy in patients with diabetes mellitus. Attempts at intense glycemic control inevitably increase the risk of hypoglycemia. Up to six-fold higher death rates have been associated with diabetes in patients who experience severe hypoglycemia than in those who do not experience severe hypoglycemia. Patients with diabetes should be screened for the risk of clinically meaningful hypoglycemia and have access to ready-to-use glucagon, ”said Dr. med. Thomas Pieber, Professor of Medicine, Chair of Endocrinology and Diabetology, Department of Internal Medicine at the Medical University of Graz in Austria.

ABOUT GVOKE / OGLUO

Gvoke  PFS and Gvoke HypoPen  (Glucagon Injection), the first prescription, ready-to-use, premixed, and pre-dosed glucagon injection, were approved by the FDA for use in the United States in September 2019. Gvoke is indicated for the treatment of severe hypoglycaemia in pediatric and adult patients with diabetes 2 years of age and older. Ogluo received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in December 2020 and the European Commission (EC) granted approval on February 11, 2021. Ogluo is used for the treatment of severe hypoglycemia in adults, Indicated for adolescents and children from 2 years of age with diabetes mellitus.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR GMOES

Gvoke is indicated for the treatment of severe hypoglycaemia in adult and pediatric patients with diabetes 2 years of age and older.

Contraindications (contraindications)

Gvoke is contraindicated in patients with pheochromocytoma, insulinoma, and known hypersensitivity to glucagon or any of the excipients in Gvoke. Allergic reactions have been reported with glucagon and include anaphylactic shock with dyspnoea and hypotension.

Warnings and Precautions

Gvoke is contraindicated in patients with pheochromocytoma because glucagon can stimulate the release of catecholamines from the tumor. If the patient develops a dramatic rise in blood pressure and a previously undiagnosed pheochromocytoma is suspected, 5 to 10 mg of phentolamine mesylate administered intravenously has been shown to be effective in lowering blood pressure.

In patients with insulinoma, administration of glucagon can cause an initial increase in blood sugar levels; however, the administration of Gvoke may directly or indirectly (by an initial rise in blood sugar levels) stimulate excessive release of insulin from an insulinoma and cause hypoglycemia. Gvoke is contraindicated in patients with insulinoma. If a patient develops symptoms of hypoglycemia after a dose of Gvoke, give glucose orally or intravenously.

Glucagon-related allergic reactions have been reported. This includes a general rash and, in some cases, anaphylactic shock with difficulty breathing and hypotension. Gvoke is contraindicated in patients with a previous hypersensitivity reaction.

Gvoke is only effective in treating hypoglycemia when there is sufficient hepatic glycogen. Patients with starvation, adrenal insufficiency, or chronic hypoglycemia may not have a sufficient amount of hepatic glycogen that administration of Gvoke will not be effective. Patients with these conditions should be treated with glucose.

Necrolytic migratory erythema (NME), a skin rash often associated with glucagonomas that resolves after the glucagon is discontinued, has been reported following continuous infusion of glucagon. Should NME occur, consideration should be given to whether the benefits of continuous infusion of glucagon outweigh the risks. Glucagon given to patients with glucagonoma can cause secondary hypoglycaemia.

Side effects

The most common (≥5%) Gvoke-related adverse reactions are nausea, vomiting, injection site edema (increased by 1 mm or more) and hypoglycaemia.

Drug interactions

In patients taking beta-blockers, the administration of OGLUO may cause transient increases in pulse and blood pressure. In patients taking indomethacin, Gvoke may lose the ability to increase blood sugar levels or even cause hypoglycemia. Gvoke may increase the anticoagulant effects of warfarin.