Saxagliptin receives European Marketing Authorization for the Treatment of T2DM

The European Medical Evaluation Authority (EMEA) has granted marketing authorization for saxagliptin (Onglyza®, Bristol-Myers Squibb and AstraZeneca )in the 27 countries of the European Union.

Saxagliptin is indicated as a once-daily 5 mg oral tablet dose as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. The drug can be used in combination with commonly prescribed oral anti-diabetic medications – such as metformin, sulfonylureas (SUs) or thiazolidinediones (TZDs).

The European marketing authorization is based on data submitted from a comprehensive clinical development program that included six core Phase III registration trials and a Phase IIIB study comparing saxagliptin plus metformin with sitagliptin plus metformin. The registration trials assessed the safety and efficacy of saxagliptin and involved 4,148 patients with type 2 diabetes, including 3,021 patients treated with saxagliptin.

Saxagliptin is the first medicine to be launched in Europe through the worldwide collaboration of Bristol-Myers Squibb and AstraZeneca to enable the companies to research, develop and commercialize select investigational medicines for the treatment of type 2 diabetes.

Béatrice Cazala, Bristol-Myers Squibb's President Europe, and President, Global Commercialization, noted: "The European Commission decision marks an important milestone in the alliance between Bristol-Myers Squibb and AstraZeneca. Our legacy in treating type 2 diabetes and cardiovascular disease, together with our knowledge and expertise, enables us to deliver to patients a medicine that will offer further choice for the treatment of this serious condition."

Ulf Sather, AstraZeneca's Regional Vice President for Europe, explained: "Diabetes is a growing epidemic currently affecting some 53 million people in Europe with the number of cases expected to increase. The approval of saxagliptin is good news for those affected by type 2 diabetes and further demonstrates the commitment of AstraZeneca and Bristol-Myers Squibb to bring much needed options for the treatment of type 2 diabetes."

The worldwide epidemic of T2DM is further emphasized by the 20.8 million people, or 7% of the U.S. population, with diabetes. By 2050, this number is projected to more than double to 48.3 million.

“Type 2 diabetes is a daily challenge for adult patients and physicians. With the FDA approval of Onglyza, physicians and adult patients with type 2 diabetes have an important new treatment to help improve glycemic control,” said David Brennan, Chief Executive Officer, AstraZeneca.

Mechanism of Action
Saxagliptin belongs to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. These are designed to enhance the body's ability to decrease blood sugar (glucose) when it is elevated by acting on the natural hormones, incretins, thereby increasing insulin production, and by reducing the liver's production of glucose.

DPP-4 inhibitors have actions similar to those of the glucagon-like peptide-1 receptor agonists (GLP-1 agonist), such as stimulation of insulin secretion, inhibition of glucagon secretion, and preservation of beta-cell function. However, DPP-4 inhibitors do not slow gastric emptying or cause weight loss. DPP-4 inhibitors raise incretin levels to normal or slightly above normal levels.The advantage of DPP-4 inhibitors is oral administration; the GLP-1 receptor agonist is injectable.

DPP-4 inhibitors are well tolerated, carry a low risk of producing hypoglycemia, and are weight neutral. Drugs belonging to this class are vildagliptin (Galvus®, marketed in the EU by Novartis), sitagliptin, saxagliptin (Bristol-Meyer Squibb, AstraZeneca and Otsuka Pharmaceutical Co), linagliptin (Boehringer Ingelheim) and alogliptin (Takeda Pharmaceutical Co). Berberine, a common herbal dietery supplement, also inhibits dipeptidyl peptidase-4, which at least partly explains its anti-hyperglycemic activities.