Results from a 24-week Phase III study presented at the 68th American Diabetes Association Annual Scientific Sessions demonstrated that saxagliptin, a selective, reversible inhibitor of the dipeptidyl peptidase (DPP-4) enzyme in development by Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN), produced significant reductions in key measures of glucose control (glycosylated hemoglobin level [A1C], fasting plasma glucose [FPG] and postprandial glucose [PPG]) in treatment naÂ¯ve people with type 2 diabetes compared to placebo (PBO). Over 24Â weeks, saxagliptin had an adverse event profile that appeared similar to placebo. The companies have proposed the trade name ONGLYZAÂ„ for saxagliptin if approved by the U.S. Food & Drug Administration.
Diabetes is a serious and chronic condition that affects nearly 21 million people in the U.S. and, unfortunately, this number is only going to rise, said Julio Rosenstock, MD,Â Director of Dallas Diabetes & Endocrine Center at Medical City, and also Clinical Professor of Medicine at University of Texas Southwestern Medical Center, Dallas, USA. New therapies need to be researched and developed to help treat this growing epidemic.
About the Study
The data represent findings from a multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 401 people with type 2 diabetes (ages 18-77) who were treatment naÂ¯ve and whose A1C level was greater than or equal to 7 percent and less than or equal to 10 percent. Individuals were randomized to one of four separate treatment arms: saxagliptin 2.5 mg (n=102), 5 mg (n=106) or 10 mg (n=98) or placebo (n=95), once daily.
The primary endpoint of the study was the change from baseline to Week 24 in A1C. The secondary endpoints of the study included achievement of A1C of less than 7 percent and changes from baseline in FPG (a measure of a personÂ™s blood glucose after at least 8 hours of fasting). PPG (a measure of a personÂ™s blood glucose, measured during an oral glucose tolerance test [OGTT]) was also evaluated.
After 24 weeks, individuals receiving ONGLYZAÂ„ (saxagliptin) 2.5 mg, 5 mg and 10 mg demonstrated a significant mean change in A1C from baseline of -0.4 percent, -0.5 percent and -0.5 percent, respectively, which resulted in a placebo-adjusted change of -0.6 percent, -0.6 percent and -0.7 percent, respectively (p-value less than 0.0001). Reductions in A1C levels were seen as early as four weeks after initiation of saxagliptin treatment, the first scheduled A1C measurement point.
The percentage of individuals receiving saxagliptin 2.5 mg, 5 mg and 10 mg or placebo who achieved the American Diabetes AssociationÂ™s recommended A1C of less than 7 percent at Week 24 was 35 percent, 38 percent and 41 percent, respectively, compared to 24 percent of individuals treated with PBO (p-value not significant at the 2.5 mg dose; p-value at the other doses less than 0.05 versus PBO). Saxagliptin demonstrated significant reductions versus placebo in FPG and PPG at all doses from baseline to Week 24.
Over 24 weeks, saxagliptin had an adverse event profile that appeared similar to placebo. Across all treatment groups, the percentage of individuals who experienced at least one adverse event was slightly higher in individuals treated with saxagliptin (75.5 percent) compared to PBO (71.6 percent). The most commonly reported (greater than or equal to 5 percent) adverse events from the saxagliptin treatment arms and PBO, respectively, were: upper respiratory tract infection [8.8 percent (27/306), 11.6 percent (11/95)]; headache [8.2 percent (25/306), 7.4 percent (7/95)], urinary tract infection [6.9 percent (21/306), 4.2 percent (4/95)], nasopharyngitis [5.9 percent (18/306), 6.3 percent (6/95)] and sinusitis [5.6 percent (17/306), 3.2 percent (3/95)].
No cases of confirmed hypoglycemia (symptoms of hypoglycemia with a fingerstick glucose less than or equal to 50Â mg/dL) were reported. The proportion of reported hypoglycemic events was similar in the saxagliptin-treatment arms (5.2 percent) and PBO (6.3 percent).
Saxagliptin was not associated with weight gain in any of the treatment groups. Mean change from baseline in body weight at Week 24 was -1.2 kg, -0.1 kg and -0.1 kg at the 2.5 mg, 5 mg and 10 mg doses, respectively, and -1.4 kg for PBO.
About ONGLYZAÂ„ (saxagliptin)
Saxagliptin, a DPP-4 inhibitor, is an investigational drug under joint development by Bristol-Myers Squibb and AstraZeneca for the treatment of type 2 diabetes. Saxagliptin is being studied in clinical trials as a once-daily therapy to determine its efficacy and safety. Saxagliptin was specifically designed to be a selective, reversible inhibitor of the DPP-4 enzyme, with dual routes of clearance. Phase III data has previously been presented in combination with metformin, the most commonly prescribed OAD, and further Phase III data, including saxagliptin added to a sulfonylurea, a thiazolidinedione and as initial combination therapy with metformin, will be disclosed later this year. The Companies plan to submit a New Drug Application (NDA) in the United States in mid 2008.
About DPP-4 Inhibitors
DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease elevated blood sugar levels (glucose) by increasing the bodyÂ™s utilization of sugar, mainly through increasing insulin production in the pancreas, and by reducing the liverÂ™s production of glucose.
About Type 2 Diabetes
Diabetes (diabetes mellitus) is a chronic disease in which the body does not produce or properly use insulin. Insulin is a hormone that is needed to convert sugar, starches (carbohydrates) and other nutrients into energy needed for daily life. The cause of diabetes continues to be investigated, and both genetic and environmental factors such as obesity and lack of exercise appear to play a role. Diabetes is associated with long-term complications that affect almost every part of the body. The disease may lead to blindness, heart and blood vessel disease, stroke, kidney failure, amputations, and nerve damage.
There are two primary underlying causes associated with type 2 diabetes: the body does not produce enough insulin (insulin deficiency), or the cells ignore the insulin (insulin resistance). Symptoms of type 2 diabetes develop gradually, and their onset is not as sudden as in type 1 diabetes. Symptoms may include fatigue, frequent urination, increased thirst and hunger, weight loss, blurred vision, and slow healing of wounds or sores. Some people, however, have no symptoms.
Type 2 diabetes is most often associated with older age, obesity, family history of diabetes, previous history of gestational diabetes, physical inactivity and certain ethnicities. People with type 2 diabetes often are characterized with: insulin resistance, abdominal obesity, a sedentary lifestyle, having low HDL-C (good) cholesterol levels and high triglyceride levels and hypertension.
Type 2 diabetes accounts for approximately 90 to 95 percent of all diabetes. This equates to roughly 221 million people with type 2 diabetes globally, and 18.7 million people in the U.S. alone.
The American Diabetes Association recommends a hemoglobin A1C measurement of less than 7 percent for most people with type 2 diabetes. Hemoglobin A1C is a measurement of a personÂ™s average blood glucose level over a two-to-three month period and is considered an important marker of long-term glucose control. Other important markers for type 2 diabetes include fasting plasma glucose, a measure of a personÂ™s blood glucose after at least 8 hours of fasting and postprandial glucose, a measure of a personÂ™s blood glucose after a meal.
Bristol-Myers Squibb and AstraZeneca Partnership
Bristol-Myers Squibb and AstraZeneca entered into a collaboration in January 2007 to enable the companies to research, develop and commercialize two investigational drugs for type 2 diabetes Â“ ONGLYZAÂ„ (saxagliptin) and dapagliflozin. 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.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life. For more information, visit www.bms.com.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that an NDA submitted to the FDA will be approved or that the timing of any NDA submission will occur as described in this release. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol-Myers Squibb’s business, including those identified in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2007, particularly under “Item 1A. Risk Factors”. Bristol- Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world’s leading pharmaceutical companies with healthcare sales of $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. In the United States, AstraZeneca is a $13.35 billion dollar healthcare business with 12,200 employees committed to improving peopleÂ™s lives. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
For more information about AstraZeneca, please visit www.astrazeneca-us.com.
AstraZeneca Forward-Looking Statement
The statements contain herein include forward-looking statements. Although we believe our expectations are based on reasonable assumptions, any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual outcomes and results to be materially different from those predicted. The forward-looking statements reflect knowledge and information available at the date of the preparation of this press release and the Company undertakes no obligation to update these forward-looking statements. Important factors that could cause actual results to differ materially from those contained in forward-looking statements, certain of which are beyond our control, include, among other things, those risk factors identified in the Company’s Annual Report/Form 20-F for 2007. Nothing contained herein should be construed as a profit forecast.
ONGLYZAÂ„ is a trademark of the Bristol-Myers Squibb Company
David M. Rosen, 609-252-5675
David Albaugh, 302-886-7098
John Elicker, 212-546-3775
Mina Blair, 44-20-7304-5084