(NYSE: BMY) and (NYSE: AZN) today announced the results of analyses showing that (saxagliptin) 5 mg demonstrated improvements across key measures of blood sugar control (glycosylated hemoglobin levels, or HbA1c; fasting plasma glucose, or FPG and post-prandial glucose, or PPG) compared to placebo in adult patients with type 2 diabetes at high risk for cardiovascular disease. These results were from a pooled, post-hoc assessment of five, 24-week, Phase III studies encompassing 1,681 patients with type 2 diabetes and varying degrees of cardiovascular risk, characterized by the presence of known risk factors or a history of cardiovascular disease. Adverse events, serious adverse events, death, discontinuation and hypoglycemia were also evaluated by various patient sub-groups. The data were presented today in two oral presentations at the 17 World Congress on Heart Disease in Toronto, Canada.
“The population of patients with type 2 diabetes who are at increased risk for cardiovascular disease was highlighted in a recently issued position statement by the American Diabetes Association and the European Association for the Study of Diabetes,” said William Cook, Ph.D., lead investigator and Global Medical Affairs manager, AstraZeneca. “These data are important because they further our understanding of the safety and efficacy of lowering blood sugar with in adult patients with type 2 diabetes who are also at risk for cardiovascular disease.”
is indicated as an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes mellitus in multiple clinical settings. should not be used for the treatment of patients with type 1 diabetes mellitus or diabetic ketoacidosis (increased levels of ketones in the blood or urine), as it would not be effective in these settings.
is contraindicated in patients with a history of a serious hypersensitivity reaction to (e.g., anaphylaxis, angioedema or exfoliative skin conditions). There have been reports of acute pancreatitis and serious hypersensitivity reactions in patients taking . If pancreatitis or a serious hypersensitivity reaction is suspected, promptly discontinue and institute appropriate medical treatment. has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for development of pancreatitis while using (saxagliptin).
When was used in combination with a sulfonylurea or with insulin (two medications known to cause hypoglycemia), the incidence of confirmed hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia when used in combination with .
In the analyses presented today, researchers found that patients taking 5 mg demonstrated glycemic improvements compared to placebo in HbA1c, FPG and two-hour PPGin a pool of patients assessed by multiple characteristics indicating increased risk of cardiovascular disease (patients with hypertension, statin use, multiple cardiovascular risk factors and previous cardiovascular disease history) across the five pooled Phase III studies at the end of 24 weeks.
Differences from placebo in adjusted mean change from baseline in HbA1c at week 24 were as follows:
In these same patient subgroups, decreases in FPG for 5 mg at week 24 ranged from -14.2 mg/dL to -16.0 mg/dL vs. placebo. Similarly, PPG results at week 24 ranged from -36.1 mg/dL to -47.0 mg/dL compared to placebo. Finally, achievement of target HbA1c (less than 7.0%) ranged from 15.7% to 21.8% versus placebo.
Rates of confirmed hypoglycemia (as defined by a glucose measurement of less than or equal to 50 mg/dL) for patients treated with (saxagliptin) 5 mg compared to placebo, respectively, across the sub-groups were as follows:
Corresponding rates of reported hypoglycemia ranged from 6.7% to 11.2% in patients treated with 5 mg vs. 6.2% to 7.2% in patients treated with placebo. The proportion of patients who experienced at least one adverse event with 5 mg ranged from 68.6% to 77.1% compared to 67.9% to 75.5% with placebo.
Data from five Phase III, randomized, placebo-controlled, 24-week studies of 5 mg were pooled for the purposes of these post-hoc analyses, with the overall objective of assessing the efficacy and safety of 5 mg compared to placebo in adult patients with type 2 diabetes and cardiovascular risk factors or a history of cardiovascular disease. Two studies evaluated 5 mg as a monotherapy in treatment-naïve patients, while three studies evaluated 5 mg as add-on therapy to other treatments including metformin, glyburide and a thiazolidinedione.Efficacy measures included change from baseline in HbA1c, FPG, 120-minute PPG and the proportion of patients achieving a therapeutic glycemic response of HbA1c that was less than 7.0%.
The analyses included 1,681 patients with type 2 diabetes (aged 18-77)with inadequate glycemic control (HbA1c inclusion criteria: 7.0% – 10.0%, 7.5% – 10.0%, 7.0% – 10.5% or greater than or equal to 7.0%). Patients were treated with 5 mg (n = 882) or placebo (n = 799), both alone or as add-on to metformin, glyburide or a thiazolidinedione.
As of July 2012, has been submitted for regulatory review in 93 countries and is approved in 78 countries including the U.S., Canada, Mexico, Europe, India, Brazil and China.
Because ketoconazole, a strong CYP3A4/5 inhibitor, increased saxagliptin exposure, the dose of should be limited to 2.5 mg when coadministered with a strong CYP3A4/5 inhibitor (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin).
In 2011, diabetes was estimated to affect more than 365 million people aged 20-79 worldwide. Because of the aging population and the growing trend of obesity, the prevalence of diabetes is projected to reach more than 550 million by 2030. Type 2 diabetes accounts for approximately 90% to 95% of all cases of diagnosed diabetes in adults. Type 2 diabetes is a chronic disease characterized by insulin resistance and dysfunction of beta cells in the pancreas, which decreases insulin sensitivity and secretion, leading to elevated glucose levels. Over time, this sustained hyperglycemia contributes to worsening insulin resistance and further beta cell dysfunction. Significant unmet needs still exist, as many patients remain inadequately controlled on their current glucose-lowering regimen.
Bristol-Myers Squibb and AstraZeneca entered into a collaboration in January 2007 to enable the companies to research, develop and commercialize select investigational drugs for type 2 diabetes. The Bristol-Myers Squibb/AstraZeneca Diabetes collaboration is dedicated to global patient care, improving patient outcomes and creating a new vision for the treatment of type 2 diabetes.
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit or follow us on Twitter at .
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: .