AstraZeneca Presents New Data Evaluating Safety and Efficacy of FARXIGA in Patients with Type 2 Diab

 AstraZeneca today announced the results of DERIVE, a Phase 3 study that evaluated the efficacy and safety of FARXIGA^®(dapagliflozin 10 mg), in patients with type 2 diabetes (T2D) with moderate renal impairment (chronic kidney disease [CKD] stage 3A with eGFR of 45-59 mL /min /1 .73m²). The results were presented at the Endocrine Society’s 100^th Annual Meeting and Expo (ENDO).

FARXIGA, an SGLT2 inhibitor, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D mellitus.¹ FARXIGA is not indicated for weight loss or for the treatment of CKD or hypertension.

The DERIVE trial randomized 321 patients with T2D (hemoglobin A1C [HbA1C] between 7-11%; mean 8.2%) and stage 3A CKD (mean estimated glomerular filtration rate [eGFR] 53 mL/min/1.73m²) from eight countries and treated them with either dapagliflozin 10 mg or placebo over 24 weeks.² The study met its primary and secondary efficacy endpoints including:

• Dapagliflozin 10 mg significantly decreased mean HbA1C (-0.37%) vs placebo (-0.03%) from baseline to week 24 (difference -0.34%, p < 0.001).

• Dapagliflozin 10 mg significantly reduced mean body weight (-3.17 kg) vs placebo (-1.92 kg) from baseline to week 24 (difference -1.25 kg, p < 0.001).

• Dapagliflozin 10 mg significantly reduced mean fasting plasma glucose (-21.46 mg/dL) vs placebo (-4.87 mg/dL) from baselines to week 24 (difference -16.6 mg/dL, p = 0.001).
• Dapagliflozin 10 mg significantly reduced mean systolic blood pressure (-4.8 mm Hg) vs placebo (-1.7 mm Hg) from baseline to week 24 (difference -3.1 mm Hg, p < 0.05).

The DERIVE trial also provides the following safety information:

• Mean eGFR was decreased at 24 weeks with dapagliflozin (-3.23 mL/min/1.73m²) vs placebo (-0.63 mL/min/1.73m²) (difference [95% CI]: -2.60 mL/min/1.73m²[−5.03 vs −0.16]).
• Overall, adverse events (AEs) occurred in 41.9% of patients with dapagliflozin and 47.8% with placebo. AEs related to study treatment by the investigators were reported in 10.6% of patients with dapagliflozin and 6.2% with placebo. The most frequent AEs related to study treatment included urinary tract infection and pollakiuria.
• No AEs of bone fracture or amputation were reported in the study.

FARXIGA is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or in patients on dialysis. FARXIGA is not recommended in patients with an eGFR persistently between 30 and <60 mL/min/1.73 m². The recommended starting dose for FARXIGA is 5 mg.

Jim McDermott, PhD, Vice President, US Medical Affairs, Diabetes at AstraZeneca, said: "We are committed to helping patients with complex and comorbid diseases like T2D and chronic kidney disease, which is demonstrated through the breadth of our research and our unique cardiovascular, renal and metabolic approach. The DERIVE study will help us learn more and provide additional data for FARXIGA in T2D."

DERIVE adds important information to previous dapagliflozin studies in patients with T2D diabetes and moderate renal impairment. AstraZeneca is planning to submit the results of DERIVE to the FDA to add to the breadth of data already contained within the existing FARXIGA Prescribing Information.

According to the Centers for Disease Control and Prevention, 30.3 million people in the US have diabetes, and T2D accounts for 90% to 95% of all diabetes cases.³ T2D is the leading cause of CKD in the US, affecting over 40% of patients, and sustaining control of diabetes can help lower patients risk of developing severe kidney disease.^{4, 5}

Important Safety Information for FARXIGA^® (dapagliflozin)

Contraindications

• Prior 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 preexisting 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

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

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.

NOTES TO EDITORS

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 main 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 the understanding of the treatment effects of our diabetes medicines in broad patient populations, as well as exploring combination products to help more patients achieve treatment success earlier in their disease.

About AstraZeneca in Cardiovascular, Renal & Metabolic Diseases

Cardiovascular, renal and metabolic diseases together form one of AstraZeneca’s main therapy areas and platforms for future growth. By following the science to understand more clearly the underlying links between the heart, kidney and pancreas, AstraZeneca is investing in the development of a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVMDs and even regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CVMD health for millions of patients worldwide.

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.

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