AstraZeneca and MedImmune present Phase II data for MEDI0382 at ADA 2018 demonstrating significant improvements in glycaemic control and weight loss in patients with type-2 diabetes

Further analysis from the Phase IIa study also underscores the potential of MEDI0382 in treating non-alcoholic fatty liver disease, with significant reduction in liver fat
 

23 June 2018
 

AstraZeneca and MedImmune, its global biologics research and development arm, today announced clinical results from a Phase IIa study of MEDI0382, an oxyntomodulin-like peptide and potential first-in-class new medicine for patients with type-2 diabetes.

The core Phase IIa data evaluating the effects of MEDI0382 on reducing blood glucose and body weight were presented at the American Diabetes Association’s (ADA) 78^th Scientific Sessions in Orlando, Florida, and simultaneously published in The Lancet. Oral presentations at ADA also featured analyses of the effects of MEDI0382 on pancreatic and incretin hormones, and on reduction in hepatic (liver) fat.

Oxyntomodulin is a peptide hormone released from the gut in a post-prandial state that activates both the GLP-1 and glucagon receptors, which are critical to controlling metabolic functions. As an oxyntomodulin-like peptide, MEDI0382’s dual targeting action is distinct from other treatment approaches. The Phase IIa data demonstrates the potential to achieve potent glucose-dependent glycaemic control, marked weight loss and reduction in liver fat with MEDI0382.¹

Cristina Rondinone, Vice President, Head of Cardiovascular, Renal and Metabolism, Innovative Medicines at MedImmune, said: “These initial results for MEDI0382 are promising, and reinforce and support further development for type-2 diabetes. With this ongoing research and evaluation of MEDI0382, AstraZeneca and MedImmune continue to be at the forefront of delivering on transformational science in cardiovascular, renal and metabolic diseases.”

Results for MEDI0382 in type-2 diabetes

In the double-blind Phase IIa study (Poster 1067-P), 51 patients with type-2 diabetes were randomized (1:1) to receive 200 µg of MEDI0382 subcutaneously, or placebo, daily. Results after six weeks of treatment showed that MEDI0382 significantly improved glycaemic control and reduced body weight compared to placebo. Specifically, results showed: 

• Marked reductions in fasting plasma glucose (-2.8 versus -1.1 mmol/L; p<0.0001) and postprandial glucose (glucose AUC0-4h, -32.8 versus -10.2; p<0.0001) from baseline with no increase in hypoglycaemia. 
• A decrease of -0.9% from baseline HbA1c levels of 7.2% to 6.3% with MEDI0382 compared to -0.6% with placebo (p=0.0004). 
• Body weight was significantly reduced with MEDI0382, with a weight loss of -3.8 kg from baseline vs. -1.7 kg with placebo (p=0.0008), and with 92% of patients treated with MEDI0382 losing more than 2 kg. 
• Treatment-related adverse events (AEs) including decreased appetite, vomiting and headache, occurred in 20 patients treated with MEDI0382 versus 15 patients treated with placebo. There were no Grade >3 AEs. Three AEs with MEDI0382 led to study discontinuation vs. one with placebo.2

A separate exploratory analysis of the Phase IIa study evaluated the effects of MEDI0382 on hepatic fat content in overweight patients with type-2 diabetes (Oral 78-OR). Results of the analysis showed patients treated with MEDI0382 showed a significant relative reduction from baseline in hepatic fat content versus placebo (-39.1% versus -19.5%; p=0.0172). The reduction in hepatic fat was also correlated with reductions in body weight and alanine aminotransferase. In addition, treatment with MEDI0382 was associated with reductions in subcutaneous adipose tissue, visceral adipose tissue and pancreatic fat, based on a post-hoc analysis.³

In an additional analysis evaluating the effects of MEDI0382 on pancreatic and incretin hormones (Oral 79-OR), results showed that MEDI0382 potentially has the capacity to increase insulin production (insulinotropic) and may also cause delayed gastric emptying. These findings help further the understanding of how MEDI0382 may potentially play a role in regulating metabolism and provide support for its continued study in the management of type-2 diabetes and other complex metabolic diseases.⁴ 

NOTES TO EDITORS 

About MEDI0382

MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1 and glucagon receptor activity. MEDI0382 was discovered and developed in MedImmune’s labs and is a dual agonist using natural amino acids. It is administered subcutaneously and is being evaluated in type-2 diabetes.  

About AstraZeneca in Cardiovascular, Renal & Metabolism (CVRM)

Cardiovascular, renal and metabolic diseases together form one of AstraZeneca’s main therapy areas and platforms for future growth. By following the science to understand more clearly the underlying links between the heart, kidney and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVRM diseases and even regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular health for millions of patients worldwide.

About MedImmune
MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology, Respiratory, Cardiovascular, Renal and Metabolic Diseases, and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centres, with additional sites in Cambridge, UK and South San Francisco, CA. For more information, please visit www.medimmune.com.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. 

For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca. 

References

^{1 Pocai, A. "Action and therapeutic potential of oxyntomodulin." Mol Metab. 2014 Jun; 3(3): 241-251.} 

^{2 Ambery, P. et al. "Robust Glucose Control and Weight Loss After 6 Weeks of Treatment with MEDI0382, a Balanced GLP-1/Glucagon Receptor Dual Agonist, in Patients with Type 2 Diabetes." American Diabetes Association Scientific Sessions 2018. Abstract #1067-P}

^{3 Jain, M. et al. "MEDI0382, a GLP-1/Glucagon Receptor Dual Agonist, Significantly Reduces Hepatic Fat Content in Subjects with Type 2 Diabetes Mellitus." American Diabetes Association Scientific Sessions 2018. Abstract #78-OR}

^{4 Parker, V. et al. "Effects of MEDI0382, a Dual Glucagon-Like Peptide-1/Glucagon Receptor Agonist, on Pancreatic and Incretin Hormones." American Diabetes Association Scientific Sessions 2018. Abstract #79-OR}