SAN DIEGO--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN) today announced results from an investigational Phase 3b clinical study which reported that ONGLYZA™ (saxagliptin) 5 mg added to insulin (with or without metformin) significantly reduced blood sugar levels (glycosylated hemoglobin levels, or HbA1c) in adult patients with type 2 diabetes compared to treatment with placebo added to insulin (with or without metformin) at 24 weeks. The results, which were presented at the 71st American Diabetes Association (ADA) Scientific Sessions in San Diego, CA, showed that the study met its primary endpoint of mean change in HbA1c from baseline to week 24.
Secondary endpoint results included a statistically significant reduction in after-meal blood sugar (post-prandial glucose, or PPG) in patients who received ONGLYZA 5 mg added to insulin (with or without metformin). In addition, there was a numerical reduction (not statistically significant) in morning blood sugar (fasting plasma glucose, or FPG) and a greater proportion of patients achieving a therapeutic glycemic response of HbA1c <7% (significance not tested) in patients who received ONGLYZA 5 mg added to insulin compared to patients who received placebo added to insulin (with or without metformin). There was also a smaller increase from baseline in mean daily insulin dose (significance not tested) in patients who received ONGLYZA 5 mg (with or without metformin). Although patients were advised not to change insulin dose, adjustments were made. It is unknown whether increased insulin doses by patients in the placebo group could have affected the magnitude of differences seen between the two treatment groups in the efficacy analyses.
A similar proportion of patients in each treatment group had at least one adverse event over the 24-week treatment period. The most common events included hypoglycemia, urinary tract infection, influenza and pain in extremity.
“Type 2 diabetes is a chronic, progressive disease and many patients who require insulin may need to increase their dosage over time to help control their blood sugar levels,” said Bernard Charbonnel, MD, Professor of Endocrinology and Metabolic Diseases at the University of Nantes, France, and principal investigator of the study. “The study showed that ONGLYZA 5 mg used with insulin helped improve HbA1c in these adult patients with type 2 diabetes.”
ONGLYZA is indicated as an adjunct to diet and exercise to improve blood sugar (glycemic) control in adults with type 2 diabetes mellitus in multiple clinical settings. ONGLYZA 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.
About The Study
The study was a 24-week multi-center, randomized, placebo-controlled, double-blind study, which evaluated the efficacy and safety of ONGLYZA when added to insulin with or without metformin compared to placebo when added to insulin with or without metformin. The study included 455 individuals with type 2 diabetes (ages 18 - 78) with inadequate glycemic control (HbA1c levels ≥ 7.5% and ≤ 11%; mean baseline HbA1c = 8.7%) currently on a stable dose of insulin (30 – 150 units/day with ≤ 20% variation per day) alone or with a stable dose of metformin for at least 8 weeks. Patients were randomly assigned to receive ONGLYZA 5 mg added to insulin (n = 304) or placebo added to insulin (n = 151) once daily for 24 weeks. A similar proportion of patients in both groups completed the study: 88.2% for the ONGLYZA added to insulin group and 88.7% for the placebo added to insulin group. Patients were advised to maintain stable insulin doses, which could be decreased to reduce risk of hypoglycemia. Patients with hyperglycemia or with substantially increased insulin had a rescue visit and remained in the study on a flexible insulin regimen. Sixty-nine percent of patients were treated with metformin, the dose of which could not be changed in the study.
The primary endpoint was mean change in HbA1c from baseline to week 24. Secondary endpoints included change from baseline in PPG, change in baseline in FPG, proportion of patients achieving a therapeutic glycemic response of HbA1c <7 % and change from baseline in mean daily insulin dose.
Study Results
Although patients were advised not to change insulin dose, adjustments were made and increased insulin doses by patients in the placebo group may have decreased the magnitude of differences seen between the two treatment groups in the efficacy analyses. After 24 weeks, individuals receiving ONGLYZA 5 mg added to insulin demonstrated the following, compared to placebo added to insulin:
- Statistically significant reduction in HbA1c from baseline, the primary endpoint of the study: -0.73% vs. -0.32% (p-value < 0.0001, n=300, baseline 8.67% for ONGLYZA 5 mg added to insulin; n=149, baseline 8.66% for placebo added to insulin)
- Similar HbA1c reduction was reported for patients receiving ONGLYZA added to insulin alone and ONGLYZA added to insulin in combination with metformin (pre-specified test of interaction, P=0.99)
- Statistically significant reduction in change from baseline in PPG (120 min PPG value in response to a meal tolerance test): -27.2 mg/dL vs. -4.2 mg/dL (p-value = 0.0016, n=262, baseline 251.2 mg/dL for ONGLYZA 5 mg added to insulin; n=129, baseline 255.1 mg/dL for placebo added to insulin)
- Numerically greater decrease in FPG from baseline: -10.08 mg/dL vs. -6.06 mg/dL
(not significant [n.s.] p-value = 0.3958, n=300, baseline 173.43 mg/dL for ONGLYZA 5 mg added to insulin; n=149, baseline 173.07 mg/dL for placebo added to insulin) - A greater proportion of patients achieving a therapeutic glycemic response of
HbA1c <7%: 17.3% (52/300) vs. 6.7% (10/149; statistical significance not tested) - Patients had an adjusted mean change from baseline in insulin of +1.7 units/day in the ONGLYZA 5 mg added to insulin group compared to an increase of +5.0 units/day for the placebo added to insulin group (statistical significance not tested; n=299, baseline 53.4U for ONGLYZA 5 mg added to insulin; n=151, baseline 55.3U for placebo added to insulin)
At week 24, 22.7% and 31.8% of patients in the ONGLYZA and placebo groups, respectively, had been rescued or discontinued due to lack of glycemic control.
A similar proportion of patients had at least one adverse event over the 24-week treatment period (56.9% in the ONGLYZA 5 mg added to insulin group vs. 59.6% in the placebo added to insulin group).
The most common adverse events for ONGLYZA 5 mg added to insulin compared to placebo added to insulin (incidence ≥ 5%) were as follows:
- Hypoglycemia (18.4% vs. 19.9%)
- Confirmed hypoglycemia with associated symptoms, with fingerstick glucose measurement of ≤ 50 mg/dL at the time of the event (5.3% vs. 3.3%)
- Urinary tract infection (5.9% vs. 6.0%)
- Influenza (3.0% vs. 6.6%)
- Pain in extremity (1.6% vs. 6.0%)
Twelve (3.9%) patients in the ONGLYZA 5 mg added to insulin group reported at least one serious adverse event (SAE), as compared to six (4.0%) patients in the placebo added to insulin group. Treatment-related SAEs were reported in two (0.7%) patients in the ONGLYZA 5 mg added to insulin group vs. zero in the placebo added to insulin group.
About ONGLYZA™(saxagliptin)
ONGLYZA was approved by the FDA in July 2009 and is indicated as an adjunct to diet and exercise to improve blood sugar (glycemic) control in adults for the treatment of type 2 diabetes mellitus in multiple clinical settings.
- ONGLYZA once daily can be used in combination with commonly prescribed oral anti-diabetic medications – metformin, glyburide (a sulfonylurea) or a thiazolidinedione (TZD) (pioglitazone or rosiglitazone) – or as a monotherapy.
- ONGLYZA should not be used for the treatment of type 1 diabetes or for the treatment of diabetic ketoacidosis.
As of May 2011, ONGLYZA has been submitted for regulatory review in more than 87 countries and is approved in 65 countries, including the U.S., Canada, Mexico, 30 European countries, India, Brazil and China.
IMPORTANT SAFETY INFORMATION for ONGLYZA™(saxagliptin)
Warnings and Precautions
- Use with Medications Known to Cause Hypoglycemia: Insulin secretagogues, such as sulfonylureas, cause hypoglycemia. Therefore, a lower dose of the insulin secretagogue may be required to reduce the risk of hypoglycemia when used in combination with ONGLYZA.
- Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with ONGLYZA or any other antidiabetic drug.
Most Common Adverse Reactions
- Most common adverse reactions (regardless of investigator assessment of causality) reported in ≥ 5% of patients treated with ONGLYZA and more commonly than in patients treated with control were upper respiratory tract infection (7.7%, 7.6%), headache (7.5%, 5.2%), nasopharyngitis (6.9%, 4.0%) and urinary tract infection (6.8%, 6.1%).
- When used as add-on combination therapy with a thiazolidinedione, the incidence of peripheral edema for ONGLYZA 2.5 mg, 5 mg, and placebo was 3.1%, 8.1% and 4.3%, respectively.
Drug Interactions
Because ketoconazole, a strong CYP3A4/5 inhibitor, increased saxagliptin exposure, the dose of ONGLYZA should be limited to 2.5 mg when coadministered with a strong CYP3A4/5 inhibitor (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir and telithromycin).
Use in Specific Populations
- Patients with Renal Impairment: The dose of ONGLYZA (saxagliptin) is 2.5 mg once daily for patients with moderate or severe renal impairment, or with end-stage renal disease requiring hemodialysis (creatinine clearance [CrCl] ≤ 50 mL/min). ONGLYZA should be administered following hemodialysis. ONGLYZA has not been studied in patients undergoing peritoneal dialysis. Assessment of renal function is recommended prior to initiation of ONGLYZA and periodically thereafter.
- Pregnant and Nursing Women: There are no adequate and well-controlled studies in pregnant women. ONGLYZA, like other antidiabetic medications, should be used during pregnancy only if clearly needed. It is not known whether saxagliptin is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when ONGLYZA is administered to a nursing woman.
- Pediatric Patients: Safety and effectiveness of ONGLYZA in pediatric patients have not been established.
Click here for U.S. Prescribing Information.
About Type 2 Diabetes
In 2010, diabetes was estimated to affect nearly 300 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 nearly 440 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. Significant unmet needs exist as nearly half of treated patients remain uncontrolled on their current glucose-lowering regimen.
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 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.
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 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 about AstraZeneca in the U.S. or our AZ&Me™ Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363).
CONTACT:
Media:
Phil McNamara, Bristol-Myers Squibb, +1 609-252-6022, [email protected]
Corey Windett, AstraZeneca, +1 302-885-0034, [email protected]
Kirsten Evraire, AstraZeneca, +1 302-885-0435, [email protected]
Investors:
John Elicker, Bristol-Myers Squibb, +1 609-252-4611, [email protected]
Karl Hard, AstraZeneca, +44-20-7304-5322, [email protected]
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