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.
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>
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.
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