Phase IIa Study Assessing Safety and Tolerability of Dapagliflozin after 14 Days as Add-on to Insuli

Phase IIa Study Assessing Safety and Tolerability of Dapagliflozin after 14 Days as Add-on to Insulin in Adult Patients with Type 1 Diabetes Presented at the 2013 American Diabetes Association Scientific Sessions ®

  • Mean daily blood glucose measured by continuous glucose monitoring (CGM) decreased with dapagliflozin on day seven; mean 7-point blood glucose trended downward in all treatment groups through day seven
  • Reductions in total daily insulin dosing at day seven were observed with dapagliflozin
  • Hypoglycemia was common in all groups and occurred more frequently with dapagliflozin

CHICAGO--(BUSINESS WIRE)-- AstraZeneca  (NYS: AZN) and Bristol-Myers Squibb Company  (NYS: BMY) today announced results from a two-week Phase IIa pilot study evaluating dapagliflozin added to insulin in 70 adult patients with sub-optimally controlled type 1 diabetes. Results from this study showed that in patients treated with dapagliflozin, no subjects discontinued due to lack of glycemic control, few genital and urinary tract infections were reported and hypoglycemia was observed in all treatment groups. In addition, mean daily blood glucose derived from 7-point glucose measurements trended downward in all treatment groups through day seven and reductions in total daily insulin dosing at day seven were observed with dapagliflozin. These findings will be presented Sunday, June 23, in a late-breaking poster session at the 73rd Scientific Sessions® of the American Diabetes Association in Chicago.

In this study, there was one case of major hypoglycemia in the dapagliflozin 10 mg group that led to discontinuation. The proportion of adverse events (excluding hypoglycemia events) was 61.5% for the placebo group and 38.5%, 46.7%, 50.0% and 40.0% for the dapagliflozin 1, 2.5, 5 and 10 mg groups added on to background insulin, respectively. The proportion of hypoglycemia events was 61.5% for the placebo group and 92.3%, 60.0%, 78.6% and 66.7% for the dapagliflozin 1, 2.5, 5 and 10 mg groups added on to background insulin, respectively. There were two cases of urinary tract infection reported (one in the placebo group and one in the dapagliflozin 2.5 mg group) and two cases of genital infections (one in the dapagliflozin 1 mg group and one in the dapagliflozin 5 mg group). One serious adverse event was reported (gastroparesis) in the dapagliflozin 5 mg group, which was not considered treatment-related, and was the only adverse event that led to discontinuation.


"Many people with type 1 diabetes may benefit from other treatment options in addition to insulin," said Robert Henry, M.D., director, Center for Metabolic Research VA San Diego Healthcare System and primary study investigator. "These preliminary data with dapagliflozin added on to insulin are encouraging and support the need for further studies."

Results of the study's exploratory objectives showed a dose-dependent increase in urine glucose excretion with dapagliflozin at day seven based on mean change from baseline (41.9, 48.5, 72.4 and 88.8 grams/24 hours for the 1, 2.5, 5 and 10 mg doses, respectively) compared with a decrease for placebo (-21.6 grams). Continuous glucose monitoring (CGM) data suggested a dose-dependent potential for reduced glycemic levels based on mean change from baseline in average daily glucose (-15.7, -13.9, -29.5 and -41.3 mg/dL for the 1, 2.5, 5 and 10 mg doses, respectively; -20.4 mg/dL for placebo). In addition, reductions in total daily insulin dosing at day seven were reported for the higher dapagliflozin doses (-19.31% for 5 mg and -16.17% for 10 mg compared to 1.66% for placebo). The investigator notes that the small population size limits the ability to interpret the data from this study.

Dapagliflozin, an investigational oral compound, is a selective and reversible inhibitor of sodium-glucose cotransporter 2 (SGLT2), which works independently of insulin. Dapagliflozin is currently approved for the treatment of type 2 diabetes in the European Union, Australia, New Zealand and Mexico. In January 2012, the U.S. Food and Drug Administration (FDA) issued a complete response letter regarding the New Drug Application (NDA) for dapagliflozin for the treatment of adults with type 2 diabetes, requesting additional clinical data to allow a better assessment of the benefit-risk profile for dapagliflozin.

"We are excited to have the opportunity to explore the potential of dapagliflozin in patients with type 1 diabetes," said Briggs Morrison, executive vice president Global Medicines Development and Chief Medical Officer, AstraZeneca. "The AstraZeneca/Bristol-Myers Squibb Diabetes Alliance is dedicated to addressing the global burden of diabetes by advancing individualized patient care and these study results, while preliminary, align with this commitment."

Study Design

This was a two-week randomized, double-blind, placebo-controlled, Phase IIa pilot study which evaluated dapagliflozin added to insulin in patients with sub-optimally controlled type 1 diabetes. Seventy adult patients on stable insulin with HbA1c 7-10% (baseline mean 8.5%) were randomized to receive dapagliflozin (1 mg, 2.5 mg, 5 mg or 10 mg) or placebo once daily for 14 days. The primary objective of the study was to assess safety and tolerability of dapagliflozin after 14 days as add-on to insulin in adult patients with type 1 diabetes. Secondary objectives included change from baseline at seven days in 7-point glucose monitoring profiles and pharmacokinetics. Exploratory objectives included change from baseline at seven days in CGM profiles and 24-hour urine glucose output.

About SGLT2 Inhibition

The kidney plays an important role in glucose balance, normally filtering ~180 g of glucose each day from circulation into urine, with virtually all of the filtered glucose subsequently being reabsorbed back into circulation by the kidney. SGLT2 is a glucose transporter found in the kidney which plays a critical role in glucose reabsorption. Selective inhibition of SGLT2 blocks reabsorption of glucose from the urine, facilitating its removal in an insulin-independent manner.

About Diabetes

In 2012, diabetes was estimated to affect more than 370 million people worldwide. The prevalence of diabetes is projected to reach more than 550 million by 2030. While type 2 diabetes accounts for approximately 90% to 95% of all cases of diagnosed diabetes in adults,type 1 diabetes is more often diagnosed in children and young adults and occurs when the body does not produce insulin.

AstraZeneca/Bristol-Myers Squibb Diabetes Alliance

Dedicated to addressing the global burden of diabetes by advancing individualized patient care, AstraZeneca and Bristol-Myers Squibb are working in collaboration to research, develop and commercialize a versatile portfolio of innovative treatment options for diabetes and related metabolic disorders that aim to provide treatment effects beyond glucose control. Find out more about the Alliance and our commitment to meeting the needs of health care professionals and people with diabetes at www.astrazeneca.com or www.bms.com.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. 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.

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.

AstraZeneca Cautionary Statement Regarding Forward-Looking Statements

In order, among other things, to utilize the 'safe harbor' provisions of the US Private Securities Litigation Reform Act 1995, we are providing the following cautionary statement: This press release contains certain forward-looking statements with respect to the operations, performance and financial condition of the Group. 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 preparation of this press release and AstraZeneca undertakes no obligation to update these forward-looking statements. We identify the forward-looking statements by using the words 'anticipates', 'believes', 'expects', 'intends' and similar expressions in such 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: the loss or expiration of patents, marketing exclusivity or trademarks, or the risk of failure to obtain patent protection; the risk of substantial adverse litigation/government investigation claims and insufficient insurance coverage; exchange rate fluctuations; the risk that R&D will not yield new products that achieve commercial success; the risk that strategic alliances and acquisitions will be unsuccessful; the impact of competition, price controls and price reductions; taxation risks; the risk of substantial product liability claims; the impact of any failure by third parties to supply materials or services; the risk of failure to manage a crisis; the risk of delay to new product launches; the difficulties of obtaining and maintaining regulatory approvals for products; the risk of failure to observe ongoing regulatory oversight; the risk that new products do not perform as we expect; the risk of environmental liabilities; the risks associated with conducting business in emerging markets; the risk of reputational damage; the risk of product counterfeiting; the risk of failure to successfully implement planned cost reduction measures through productivity initiatives and restructuring programs; the risk that regulatory approval processes for biosimilars could have an adverse effect on future commercial prospects; and the impact of increasing implementation and enforcement of more stringent anti-bribery and anti-corruption legislation. Nothing in this press release should be construed as a profit forecast.

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 in the U.S. or, if approved, that it will become commercially successful. There is also no guarantee that the additional studies of the currently-approved product described in this release will lead to additional approved indications for the 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, 2012, 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.



Media:
Shelly Mittendorf, Bristol-Myers Squibb, 609-480-2951, shelly.mittendorf@bms.com
Kristin Rogers, AstraZeneca, 302-885-8922, kristin.rogers@astrazeneca.com
or
Investors:
John Elicker, Bristol-Myers Squibb, 609-252-4611, john.elicker@bms.com
Karl Hard, AstraZeneca, 44-20-7604-8123, karl.j.hard@astrazeneca.com

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