FDA approves once-daily QTERN® (dapagliflozin and saxagliptin) tablets for adults with type-2 diabetes

QTERN fixed-dose combination will provide an additional oral medicine option for patients taking FARXIGA® (dapagliflozin) to improve blood sugar level

AstraZeneca (NYSE:AZN) today announced that the US Food and Drug Administration (FDA) has approved once-daily QTERN® (10mg dapagliflozin and 5mg saxagliptin) for the treatment of type-2 diabetes. The new medicine is indicated as an adjunct to diet and exercise to improve glycemic (blood sugar level) control in adults with type-2 diabetes who have inadequate control with dapagliflozin (10mg) or who are already treated with dapagliflozin and saxagliptin.

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development at AstraZeneca, said: "Type-2 diabetes is a complex disease that is at epidemic proportions, affecting more than 29 million people in the US alone. The approval of QTERN is good news for patients who may benefit from improved glycemic control by adding a DPP-4 inhibitor to a SGLT-2 inhibitor in a convenient once-daily tablet.”

SGLT-2 inhibitors help patients achieve improved glycemic control by reducing the reabsorption of glucose from the blood and enabling its removal via the urine. SGLT-2 inhibitors, including FARXIGA® (dapagliflozin), have demonstrated reductions in HbA1c and have also been shown to reduce weight and blood pressure. DPP-4 inhibitors reduce blood glucose as measured by HbA1c. FARXIGA is not indicated for weight loss or the treatment of hypertension.

QTERN is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. QTERN is contraindicated in patients with prior serious hypersensitivity reaction to QTERN or its components, patients with moderate to severe renal impairment, end stage renal disease, or on dialysis. The most common adverse reactions experienced were upper respiratory tract infection, urinary tract infection, and dyslipidemia.

INDICATION AND LIMITATIONS OF USE for QTERN® (dapagliflozin and saxagliptin)
QTERN is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) who have inadequate control with dapagliflozin or who are already treated with dapagliflozin and saxagliptin.

QTERN is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. QTERN should only be used in patients who tolerate 10 mg dapagliflozin.

IMPORTANT SAFETY INFORMATION for QTERN® (dapagliflozin and saxagliptin)

Contraindications

  • Prior serious hypersensitivity reaction to QTERN or its components
  • Moderate to severe renal impairment (eGFR <45 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis

Warning and Precautions

  • Pancreatitis: There have been postmarketing reports of acute pancreatitis in patients taking saxagliptin, and in the SAVOR cardiovascular outcomes trial. Observe for pancreatitis. If pancreatitis is suspected, discontinue QTERN
  • Heart Failure: In the SAVOR cardiovascular outcomes trial, more patients treated with saxagliptin were hospitalized for heart failure compared to placebo. Patients with a prior history of heart failure or renal impairment had a higher risk for hospitalization for heart failure. Consider the risks and benefits of QTERN in patients who have known risk factors for heart failure. Monitor for signs and symptoms. If heart failure develops, consider discontinuation of QTERN
  • Hypotension: Dapagliflozin causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating QTERN in patients with impaired renal function, elderly patients, or patients on loop diuretics. Do not initiate QTERN in patients with an eGFR <60 mL/min/1.73 m2. Monitor for hypotension
  • Ketoacidosis has been reported in patients with type 1 and type 2 diabetes receiving dapagliflozin. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue QTERN, evaluate and treat promptly. Before initiating QTERN, consider risk factors for ketoacidosis. Patients on QTERN may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
  • Acute Kidney Injury and Impairment in Renal Function: Dapagliflozin causes intravascular volume contraction and renal impairment, with reports of acute kidney injury requiring hospitalization and dialysis. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue and promptly treat

        Dapagliflozin increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Before initiating QTERN, evaluate renal function and monitor periodically. Discontinue QTERN in patients if eGFR falls persistently below 60 mL/min/1.73 m2

  • Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections (UTIs) and serious UTIs have been reported with dapagliflozin. Evaluate for signs and symptoms of UTIs and treat promptly
  • Hypoglycemia: QTERN can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with QTERN
  • Hypersensitivity Reactions: Serious reactions have been reported in patients treated with saxagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with saxagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue QTERN. Use caution in patients with a history of angioedema to another DPP-4 inhibitor
  • Genital Mycotic Infections: Dapagliflozin increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
  • Increases in Low-Density Lipoprotein Cholesterol (LDL-C) occur with dapagliflozin. Monitor LDL-C and treat per standard of care
  • Bladder cancer: An imbalance in bladder cancers was observed in clinical trials. There were too few cases to determine whether the emergence of these events is related to dapagliflozin, and insufficient data to determine whether dapagliflozin has an effect on pre-existing bladder tumors. QTERN should not be used in patients with active bladder cancer. Use with caution in patients with a history of bladder cancer
  • Severe and Disabling Arthralgia has been reported in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider discontinuing drug if appropriate
  • Bullous Pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If suspected, discontinue QTERN
  • Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with QTERN

Adverse Reactions
Most common adverse reactions reported in ≥5% of patients treated with 10 mg dapagliflozin and 5 mg saxagliptin were upper respiratory tract infection (13.6%), urinary tract infection (5.7%), and dyslipidemia (5.1%).

Drug Interactions
Strong CYP3A4/5 inhibitors (eg, ketoconazole): Coadministration with QTERN significantly increases saxagliptin concentrations. Do not coadminister QTERN.

Use in Specific Populations

  • Pregnancy: Advise females of the potential risk to a fetus especially during the second and third trimesters
  • Lactation: QTERN is not recommended when breastfeeding

Please click here for US Full Prescribing Information and Medication Guide for QTERN.  

INDICATION AND LIMITATIONS OF USE for FARXIGA® (dapagliflozin)
FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin)

Contraindications

  • History of a serious hypersensitivity reaction to FARXIGA
  • Severe renal impairment (eGFR <30 mL/min/1.73 m2), end stage renal disease, or patients on dialysis

Warnings and Precautions

  • Hypotension: FARXIGA causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating FARXIGA in.patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for hypotension
  • Ketoacidosis has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
  • Acute Kidney Injury and Impairment in Renal Function: FARXIGA causes intravascular volume contraction and renal impairment, with reports of acute kidney injury requiring hospitalization and dialysis. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue and promptly treat. FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Before initiating FARXIGA, evaluate renal function and monitor periodically. FARXIGA is not recommended in patients with an eGFR persistently between 30 and <60 mL/min/1.73 m2
  • Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections [UTIs] and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
  • Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
  • Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
  • Increases in Low-Density Lipoprotein Cholesterol (LDL-C) occur with FARXIGA. Monitor LDL-C and treat per standard of care
  • Bladder cancer: An imbalance in bladder cancers was observed in clinical trials. There were too few cases to determine whether the emergence of these events is related to FARXIGA, and insufficient data to determine whether FARXIGA has an effect on pre- existing bladder tumors. FARXIGA should not be used in patients with active bladder cancer. Use with caution in patients with a history of bladder cancer
  • Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with FARXIGA

Adverse Reactions
In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).

Use in Specific Populations

  • Pregnant Women: There are no adequate and well-controlled studies of FARXIGA in pregnant women. Consider appropriate alternative therapies, especially during the second and third trimesters. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus
  • Nursing Mothers: Discontinue FARXIGA or discontinue nursing

Please click here for US Full Prescribing Information and Medication Guide for FARXIGA.

NOTES TO EDITORS

About QTERN
QTERN combines two anti-hyperglycemic agents with complementary mechanisms of action in a once-daily tablet: Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor; and saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. The FDA approved QTERN based on data from a 24-week, Phase III, multi-center, randomized, double-blind, placebo-controlled trial (n=315) designed to evaluate the efficacy and safety of saxagliptin added to dapagliflozin in adult patients with type-2 diabetes who experienced inadequate glycemic control (HbA1c ≥7% to ≤10.5%) with metformin (≥1,500 mg per day). The safety of combined use of dapagliflozin and saxagliptin has been evaluated in a pooled safety analysis (N=1,169; 492 treated with QTERN) of three Phase III placebo-controlled clinical trials for up to 52 weeks.

About AstraZeneca in Diabetes
AstraZeneca is pushing the boundaries of science with the goal of developing life-changing medicines that aim to reduce the global burden and complications of diabetes. As a core therapy area for the company, we are focusing our research and development efforts on diverse populations and patients with significant co-morbidities, such as cardiovascular disease, obesity, non-alcoholic steatohepatitis (NASH), and chronic kidney disease.

Our commitment to diabetes is exemplified by the depth and breadth of our global clinical research program. This commitment is advancing understanding of the treatment effects of our diabetes medicines in broad patient populations, as well as exploring combination product approaches to help more patients achieve treatment success earlier in their disease progression. Our ambition is to reduce the long-term impact of diabetes.

About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

CONTACTS

Media Inquiries

Michele Meixell                    +1 302 885 2677
Abigail Bozarth                    +1 302 885 2677

 

3336704  3/17