PRINCETON, N.J. & WILMINGTON, Del.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN) today announced that the U.S. Food and Drug Administration has approved the inclusion of data from two clinical studies in an update to the ONGLYZA™ (saxagliptin) U.S. Prescribing Information for adult type 2 diabetes patients.
The renal study investigated the safety and efficacy of ONGLYZA in patients with moderate to severe renal impairment or end-stage renal disease (ESRD). The 12-week data showed that ONGLYZA 2.5 mg once daily significantly improved glycoslated hemoglobin (HbA1c) from baseline compared to placebo when added to patients’ current diabetes treatment. In patients with ESRD, ONGLYZA and placebo showed numerically comparable reductions in HbA1c. This finding is inconclusive because the trial was not adequately powered to show efficacy within specific subgroups of renal impairment. The incidence of adverse events was similar between ONGLYZA and placebo.
The data from a separate 52-week study comparing ONGLYZA to titrated glipizide in patients with inadequate glycemic control on metformin therapy plus diet and exercise showed that ONGLYZA plus metformin provided similar HbA1c reductions from baseline. This conclusion may be limited to patients with baseline HbA1c comparable to those in the trial. ONGLYZA plus metformin also resulted in significantly less confirmed hypoglycemia, as well as weight loss compared to weight gain, versus titrated glipizide plus metformin.
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 type 1 diabetes or for the treatment of diabetic ketoacidosis (dangerously high levels of ketones in the blood or urine).
“Many people with type 2 diabetes also experience kidney impairment, which can limit treatment options. With this update, ONGLYZA now includes efficacy and safety data in its label supporting its use in this important population,” said Elliott Sigal, M.D., Ph.D., executive vice president, chief scientific officer and president, Research & Development, Bristol-Myers Squibb. “The study comparing ONGLYZA to titrated glipizide provides further evidence for the use of ONGLYZA as an add-on therapy to metformin.”
If used with an insulin secretagogue such as a sulfonylurea, a lower dose of the insulin secretagogue may be required to reduce the risk of hypoglycemia. There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with ONGLYZA or any other antidiabetic drug.
Efficacy and safety of ONGLYZA in type 2 diabetes patients with renal impairment
A total of 170 adult patients participated in a 12-week, randomized, double-blind, placebo-controlled trial. The study was conducted to evaluate the efficacy and safety of ONGLYZA 2.5 mg once daily compared with placebo in patients with type 2 diabetes and moderate (n=90) or severe (n=41) renal impairment or ESRD (n=39). In this trial, 98% of patients were using background anti-diabetic medications (75% were using insulin and 31% were using oral anti-diabetic medications, mostly sulfonylureas).
After 12 weeks of treatment, ONGLYZA 2.5 mg once daily provided significant improvement in HbA1c compared to placebo. The ONGLYZA 2.5 mg group (mean baseline HbA1c 8.4%) demonstrated a greater adjusted mean change in HbA1c from baseline of -0.9% compared to -0.4% for placebo (mean baseline HbA1c 8.1%; p<0.01). In the subgroup of patients with ESRD, ONGLYZA and placebo resulted in comparable reductions in HbA1c from baseline to Week 12. This finding is inconclusive because the trial was not adequately powered to show efficacy within specific subgroups of renal impairment.
The incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between ONGLYZA and placebo. The overall incidence of reported hypoglycemia was similar between treatment groups (20% for ONGLYZA 2.5 mg versus 22% for placebo). Four ONGLYZA-treated patients (4.7%) and three placebo-treated patients (3.5%) reported at least one episode of confirmed symptomatic hypoglycemia (fingerstick glucose ≤50 mg/dL).
The dose of ONGLYZA is 2.5 mg once daily for patients with moderate or severe renal impairment, or with ESRD requiring hemodialysis (creatinine clearance [CrCl] ≤50mL/min). In patients requiring hemodialysis, ONGLYZA should be administered following hemodialysis. ONGLYZA has not been studied in patients undergoing peritoneal dialysis. No dosage adjustment for ONGLYZA 5 mg is recommended for patients with mild renal impairment (CrCl >50 mL/min). Assessment of renal function is recommended prior to initiation of ONGLYZA and periodically thereafter.
Efficacy and safety of ONGLYZA plus metformin vs. titrated glipizide plus metformin in type 2 diabetes patients
In a 52-week, randomized, double-blind, active-controlled study of 858 adult patients with type 2 diabetes and inadequate glycemic control, ONGLYZA (n=428; mean baseline HbA1c 7.7%) and titrated glipizide (n=430; mean baseline HbA1c 7.6%) resulted in similar mean reductions from baseline in HbA1c when added to metformin therapy. This conclusion may be limited to patients with baseline HbA1c comparable to those in the trial (91% of patients had baseline HbA1c of <9%). After 52 weeks of treatment, patients treated with ONGLYZA 5 mg (mean baseline body weight 196 lbs) exhibited a statistically significant decrease from baseline in mean body weight (-2.4 lbs) compared to a mean weight gain (+2.4 lbs) in patients administered titrated glipizide (p<0.0001).
More than two-thirds of patients in the glipizide plus metformin group underwent two or three glipizide dose titrations, with a mean final daily dose of 15 mg.
Twelve times fewer ONGLYZA 5 mg plus metformin patients vs. glipizide plus metformin patients experienced a hypoglycemic event: 3.0% (19 events in 13 patients) vs. 36.3% (750 events in 156 patients), respectively. Confirmed symptomatic hypoglycemia (accompanying fingerstick blood glucose ≤50 mg/dL) was reported in none of the ONGLYZA-treated patients and in 35 of the glipizide-treated patients (8.1%; p<0.0001). After 52 weeks, excluding hypoglycemia, 60.0% of patients taking ONGLYZA 5 mg plus metformin experienced an adverse event compared to 56.7% of patients who received titrated glipizide plus metformin. Serious adverse events occurred in 9.1% vs. 7.4% of patients who received ONGLYZA 5 mg plus metformin vs. titrated glipizide plus metformin, respectively.
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 to significantly reduce HbA1c levels.
- ONGLYZA (saxagliptin) should not be used for the treatment of type 1 diabetes or for the treatment of diabetic ketoacidosis.
ONGLYZA has been submitted for regulatory review in more than 87 countries and is approved in 56 countries, including the United States, Canada, Mexico, 30 European countries, Chile, India, Brazil, Argentina and Switzerland.
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.
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.
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.
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).
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ONGLYZA is a trademark of the Bristol-Myers Squibb Company.
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