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FDA Approves Saxagliptin for the Treatment of Type 2 Diabetes Mellitus

PRINCETON, N.J. & LONDON--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN) today announced that the U.S. Food and Drug Administration (FDA) approved ONGLYZA™ (saxagliptin), a dipeptidyl peptidase-4 (DPP4) inhibitor. ONGLYZA 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. ONGLYZA once daily can be used in combination with commonly prescribed oral anti-diabetic medications – metformin, sulfonylureas or thiazolidinediones (TZD) – or as a monotherapy to significantly reduce glycosylated hemoglobin (A1C) levels. ONGLYZA should not be used for the treatment of type 1 diabetes or for the treatment of diabetic ketoacidosis (high levels of certain acids, known as ketones, in the blood or urine). ONGLYZA has not been studied in combination with insulin.

Nearly Half of All Adult Patients with Type 2 Diabetes Remain Uncontrolled on Their Current Therapy
“The FDA approval of ONGLYZA is an important development for adult patients with type 2 diabetes struggling every day to control their blood sugar levels. Nearly half of adult patients remain uncontrolled on their current treatment regimen and may thus require additional medications,” said Elliott Sigal, M.D., Ph.D, executive vice president, chief scientific officer, and president, Research & Development, Bristol-Myers Squibb. “Our ongoing clinical trial program has demonstrated that ONGLYZA showed improved A1C control both in combination and monotherapy settings.”

“Type 2 diabetes is a daily challenge for adult patients and physicians. With the FDA approval of ONGLYZA, physicians and adult patients with type 2 diabetes have an important new treatment to help improve glucose control,” said David Brennan, chief executive officer, AstraZeneca. “ONGLYZA is the product of a major collaboration between AstraZeneca and Bristol-Myers Squibb to further the understanding of how best to treat this challenging disease and help adult patients achieve their treatment goals.”

ONGLYZA™ (saxagliptin) Clinical Development Program
The approval is based on a clinical development program, which included approximately 5,000 individuals, more than 4,000 of whom received ONGLYZA. As part of the development program, ONGLYZA, with diet and exercise, was studied as add-on therapy with other oral anti-diabetic medications, including metformin, the sulfonylurea glyburide and TZDs; in adult patients new to diabetes therapy starting metformin and ONGLYZA together; and as a monotherapy. Throughout the Phase III development program, treatment with ONGLYZA at all doses produced clinically relevant and statistically significant reductions in all three key measures of glucose control studied – A1C, fasting plasma glucose (FPG) and post-prandial glucose (PPG) – when partnered with other commonly used oral anti-diabetic agents (metformin, sulfonylureas and TZDs), or when used as a monotherapy. ONGLYZA was weight and lipid neutral compared to placebo.

ONGLYZA Provides A1C Control Through Effects on Both FPG and PPG
Incretin hormones help the body regulate glucose levels in response to meals by influencing the pancreatic secretion of insulin and glucagon. ONGLYZA increases and prolongs the action of incretin hormones by inhibiting the DPP4 enzyme that inactivates incretins usually within minutes. The inhibition of the DPP4 enzyme by ONGLYZA results in an increase in the production of insulin and a decrease in the production of glucagon by the pancreas. These effects are glucose dependent and enhance the body’s natural response to food to reduce blood sugar levels before and after meals.

“I continue to see adult patients in my practice who, despite treatment, still have high FPG or high PPG, both of which are key contributors to elevated A1C," said Robert Henry, M.D., Chief, Endocrinology & Metabolism, University of California, San Diego. "The approval of saxagliptin provides a new treatment for adult patients with type 2 diabetes that helps to reduce A1C levels by working across key glucose measures to improve glycemic control.”

ONGLYZA Complements Metformin to Provide Statistically Significant A1C Reductions
ONGLYZA was studied extensively with metformin, the most commonly-prescribed oral anti-diabetic medication. In adult patients inadequately controlled on metformin, the addition of ONGLYZA 2.5 mg (n=192, baseline A1C 8.1 percent) and 5 mg (n=191, baseline A1C 8.1 percent) once daily reduced A1C levels from baseline to Week 24 by -0.6 percent and –0.7 percent respectively for ONGLYZA™ (saxagliptin) vs. +0.1 percent increase for placebo (p For those new to diabetes medications, the use of ONGLYZA 5 mg with metformin (n=320, baseline A1C 9.4 percent) as initial therapy lowered A1C from baseline to week 24 by -2.5 percent vs. -2 percent for metformin plus placebo (p Complementary and Statistically Significant A1C Reductions When Added to the Sulfonylurea Glyburide or TZDs
ONGLYZA also offered better glucose control for adult patients currently uncontrolled on glyburide. The addition of ONGLYZA 2.5 mg (n=248, baseline A1C 8.4 percent) or 5 mg (n=253, baseline A1C 8.5 percent) to a submaximal total daily dose of glyburide 7.5 mg reduced A1C levels from baseline at week 24 by -0.5 percent and -0.6 percent, respectively for ONGLYZA vs. +0.1 percent increase with an approximate doubling of the total daily dose of the glyburide plus placebo (p When used in addition to TZDs (pioglitazone or rosiglitazone), ONGLYZA™ (saxagliptin) offered additional glucose control. The addition of ONGLYZA 2.5 mg (n=195, baseline A1C 8.3 percent) and 5 mg (n=186, baseline A1C 8.4 percent) reduced A1C levels from baseline at week 24 by -0.7 percent and -0.9 percent, respectively vs. –0.3 percent for placebo (p ONGLYZA Provides Significant A1C Reduction When Used as Monotherapy
When studied as a monotherapy, ONGLYZA significantly improved glucose control, with a difference in A1C from baseline of -0.4 percent and -0.5 percent for ONGLYZA 2.5 mg (n=102, baseline A1C 7.9 percent) and 5 mg (n=106, baseline A1C 8.0 percent), respectively, vs. +0.2 percent increase for placebo (p ONGLYZA had an Overall Incidence of Side Effects Similar to Placebo
In clinical trials, the overall incidence of side effects for ONGLYZA 2.5 mg and 5 mg was similar to placebo (72 percent and 72.2 percent vs. 70.6 percent, respectively). The most common events reported with ONGLYZA 5 mg (≥5 percent and more commonly than placebo) were upper respiratory tract infection (7.7 percent vs. 7.6 percent, respectively), urinary tract infection (6.8 percent vs. 6.1 percent, respectively) and headache (6.5 percent vs. 5.9 percent, respectively). In adult patients treated with ONGLYZA 2.5 mg, only headache (6.5 percent) was reported at ≥5 percent and more commonly than in adult patients treated with placebo. Discontinuation of therapy due to adverse events occurred in 2.2 percent, 3.3 percent, and 1.8 percent of patients receiving ONGLYZA 2.5 mg, ONGLYZA 5 mg, and placebo, respectively. There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA.

ONGLYZA™ (saxagliptin) Offers Convenient Once Daily Dosing
ONGLYZA offers convenient, once-daily dosing of 2.5 mg or 5 mg that can be taken regardless of meals.

ONGLYZA 2.5 mg is recommended for adult patients with moderate or severe renal impairment, or end-stage renal disease requiring hemodialysis (creatinine clearance less ≤50 mL/min). ONGLYZA has not been studied in patients undergoing peritoneal dialysis. Assessment of renal function is recommended prior to initiation of ONGLYZA and periodically thereafter.

The dose for ONGLYZA should be limited to 2.5 mg when coadministered with strong cytochrome P450 3A4/5 (CYP 3A4/5) inhibitors (e.g., ketoconazole).

No dose adjustment is required based on gender, race, weight or hepatic impairment.

Source: Bristol-Myers Squibb

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