New Data Show Investigational Compound Dapagliflozin When Added to Glimepiride Maintained Reductions in Blood Sugar Levels in Adults with Type 2 Diabetes Over 48 Weeks of Treatment

Update: Farxiga (dapagliflozin) Now FDA Approved - January 8, 2014

DUBAI, United Arab Emirates--(BUSINESS WIRE)--Dec 8, 2011 - Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN) today announced results from a Phase 3 clinical study which showed that reductions in blood sugar levels (glycosylated hemoglobin levels, or HbA1c) seen at 24 weeks with the investigational compound dapagliflozin added to existing glimepiride (sulphonylurea) therapy, compared to placebo added to glimepiride, were maintained at 48 weeks in adults with type 2 diabetes. These results, presented during the International Diabetes Federation (IDF) 2011 World Diabetes Congress in Dubai, UAE, are from a 24-week extension period of a 24-week trial. The initial 24-week results were presented at the 46th European Association for the Study of Diabetes (EASD) Annual Meeting in Stockholm, Sweden in September 2010.

In addition to maintaining reductions in blood sugar levels, the 48-week study reported that patients taking dapagliflozin added to glimepiride maintained reductions in fasting plasma glucose levels (FPG), post-prandial glucose (PPG) and total body weight.

Events suggestive of genital infections were more common in patients taking dapagliflozin added to glimepiride compared to placebo added to glimepiride. Events suggestive of urinary tract infections were similar for dapagliflozin and placebo groups in this trial. These events were proactively monitored and were generally mild to moderate in intensity, with most patients responding to standard treatment.

“Given that patients with type 2 diabetes often need multiple therapies to help manage blood sugar levels over the course of this progressive disease, it is important to assess the ability of new compounds to work in combination with commonly prescribed anti-diabetic treatments,” said Krzysztof Strojek, M.D., Department of Internal Diseases, Diabetology and Nephrology, Silesian Medical University (Poland). “This study demonstrated that the addition of dapagliflozin to existing glimepiride therapy maintained reductions in blood sugar levels over 48 weeks.”

Dapagliflozin, an inhibitor of SGLT2, a target in the kidney, is under joint development by Bristol-Myers Squibb and AstraZeneca. Dapagliflozin, as an adjunct to diet and exercise, is being investigated to evaluate its safety and efficacy in improving glycemic control in adults with type 2 diabetes, for use as a monotherapy and in combination with other anti-diabetic agents. A Marketing Authorisation Application (MAA) was validated by the European Medicines Agency (EMA) in January 2011. In March 2011, the U.S. Food and Drug Administration (FDA) accepted for review a New Drug Application (NDA) for dapagliflozin for the treatment of adults with type 2 diabetes mellitus. The FDA Prescription Drug User Fee Act (PDUFA) date is January 28, 2012.

About the Study

This was a 24-week Phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with a 24-week extension. The primary endpoint at 24 weeks was mean change in HbA1c from baseline of dapagliflozin (2.5 mg, 5 mg or 10 mg per day) added to glimepiride (4 mg/day) compared to placebo added to glimepiride. The 24-week extension was designed to assess the maintenance of efficacy of dapagliflozin added to glimepiride, as well as safety and tolerability, over 48 weeks of treatment compared to placebo added to glimepiride in adults with type 2 diabetes.

The study included 592 adults with type 2 diabetes (aged ‰¥ 18 years) with inadequate glycemic control (HbA1c ‰¥ 7% and ‰¤ 10%). Individuals were randomized to receive either dapagliflozin (2.5 mg [n=154], 5 mg [n=142] or 10 mg [n=151] per day) or placebo (n=145) added to glimepiride (4 mg per day).

There were 546 patients when the 24-week extension period began, and of these, 519 patients completed the extension.

Study Results

At the end of 48 weeks, patients taking dapagliflozin 2.5 mg, 5 mg and 10 mg added to glimepiride demonstrated the following mean improvements compared to patients taking placebo added to glimepiride:

 

  • HbA1c: -0.37% (95% CI: -0.60, -0.14), -0.53% (95% CI: -0.75, -0.30) and -0.70% (95% CI: -0.92, -0.47), respectively
  • FPG: -1.07 mmol/L (95% CI: -1.59, -0.55), -1.06 mmol/L (95% CI: -1.57, -0.54) and -1.74 mmol/L (95% CI: -2.24, -1.24), respectively
  • 2-hour PPG: -0.88 mmol/L (95% CI: -2.00, 0.24), -1.38 mmol/L (95% CI: -2.49, -0.27) and -1.20 mmol/L (95% CI: -2.26, -0.14), respectively
  • Body weight: -0.59 kg (95% CI: -1.46, 0.28), -0.76 kg (95% CI: -1.63, 0.11) and -1.64 kg (95% CI: -2.48, -0.79), respectively

Over the 48-week treatment period, the proportion of patients experiencing at least one adverse event was 58.4%, 60.7% and 58.9% for dapagliflozin 2.5 mg, 5 mg and 10 mg added to glimepiride, respectively, compared to 55.5% for placebo added to glimepiride. The most common adverse events (‰¥ 3% in any group) were as follows for dapagliflozin 2.5 mg, 5 mg and 10 mg added to glimepiride compared to placebo added to glimepiride:

 

  • Nasopharyngitis (3.9%, 7.6%, 6.6% vs. 6.8%)
  • Back pain (1.9%, 2.1%, 4.6% vs. 2.7%)
  • Upper respiratory tract infection (3.2%, 4.8%, 4.6% vs. 2.7%)
  • Bronchitis (1.3%, 2.8%, 3.3% vs. 0.7%)
  • Cough (0.6%, 1.4%, 3.3% vs. 1.4%)
  • Urinary tract infection (3.2%, 2.8%, 4.0% vs. 4.8%)
  • Dyslipidemia (3.2%, 1.4%, 2.6% vs. 0%)
  • Hypertension (5.8%, 3.4%, 2.0% vs. 6.8%)
  • Arthralgia (5.2%, 0%, 2.0% vs. 3.4%)
  • Diarrhea (2.6%, 2.8%, 0.7% vs. 4.8%)
  • Dyspepsia (1.3%, 2.8%, 0.7% vs. 3.4%)

The proportion of patients experiencing at least one serious adverse event was 10.4%, 11.0% and 8.6% for dapagliflozin 2.5 mg, 5 mg and 10 mg added to glimepiride, respectively, compared to 8.9% for placebo added to glimepiride. The proportion of patients who discontinued due to adverse events was 3.2%, 3.4% and 2.6% for dapagliflozin 2.5 mg, 5 mg and 10 mg groups, respectively, compared to 3.4% for the placebo group. There were two deaths in the dapagliflozin 2.5 mg group and one in the dapagliflozin 10 mg group, all of which were considered unrelated to treatment.

Hypoglycemic events were more frequent in the dapagliflozin groups (9.7% in 2.5 mg group, 10.3% in 5 mg group, 11.3% in 10 mg group) compared to the placebo group (6.8%), with no patients discontinuing treatment due to hypoglycemia. There was one major episode of hypoglycemia in the dapagliflozin 2.5 mg group.

The percentage of patients with events suggestive of genital infections was higher for dapagliflozin added to glimepiride compared to placebo added to glimepiride, as follows: 5.2% with dapagliflozin 2.5 mg, 6.2% with dapagliflozin 5 mg and 8.6% for dapagliflozin 10 mg compared to 1.4% with placebo added to glimepiride. Overall, events suggestive of genital infections were higher in females than in males.

The percentage of patients with events suggestive of urinary tract infections was similar across treatment groups, as follows: 4.5% with dapagliflozin 2.5 mg, 7.6% with dapagliflozin 5 mg and 7.9% for dapagliflozin 10 mg compared to 7.5% with placebo added to glimepiride. Overall, events suggestive of urinary tract infections were higher in females than in males.

No kidney infections were reported in the study.

About Type 2 Diabetes

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, progressive disease characterized by insulin resistance and/or 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. To date, treatments for type 2 diabetes have focused primarily on insulin-dependent mechanisms. An approach that acts independently of insulin could provide an additional option for adults with type 2 diabetes.

Significant unmet needs exist as nearly half of treated patients remain uncontrolled on their current glucose-lowering regimen. Many patients with type 2 diabetes have additional co-morbidities (such as obesity) which may complicate glycemic control.

About SGLT2 Inhibition

The kidney plays an important role in glucose balance, normally filtering ~180 g of glucose each day, with virtually all glucose being reabsorbed back into circulation. SGLT2 is the major sodium-glucose cotransporter in the kidney and is an insulin-independent pathway for the reabsorption of glucose back into the blood.

Bristol-Myers Squibb and AstraZeneca Collaboration

Bristol-Myers Squibb and AstraZeneca entered into a collaboration in January 2007 to enable the companies to research, develop and commercialise 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.

About Bristol-Myers Squibb

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 www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation 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: www.astrazeneca.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 dapagliflozin will receive regulatory approval or, if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. 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 Forward-Looking Statement

The statements contained 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 and Form 20-F Information 2010. Nothing contained herein should be construed as a profit forecast.

 

Contact: Media:
Bristol-Myers Squibb
Phil McNamara, +1-609-240-3739
phil.mcnamara@bms.com
or
AstraZeneca
Rachelle Benson, +1-302-885-5853
rachelle.benson@astrazeneca.com
or
Kirsten Evraire, +1-302-885-0435
kirsten.evraire@astrazeneca.com
Investors:
Bristol-Myers Squibb
John Elicker, +1-609-252-4611
john.elicker@bms.com
or
AstraZeneca
Karl Hard, +44-20-7604-8123
karl.j.hard@astrazeneca.com

 

 

Posted: December 2011

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