AstraZeneca to Present Pivotal Roxadustat Phase III Data at the American Society of Nephrology Kidney Week 2019

AstraZeneca will present pooled efficacy and cardiovascular safety analyses from the Phase III clinical program of roxadustat for the treatment of anemia from chronic kidney disease (CKD) in non dialysis-dependent (NDD) or dialysis-dependent (DD) patients.

The data are among an unprecedented 41 AstraZeneca abstracts including three late-breakers, accepted for oral and poster presentation at the American Society of Nephrology (ASN) Kidney Week 2019, which takes place from November 5 to November 10 in Washington, D.C.

The pooled efficacy and safety analyses add to the growing body of evidence on roxadustat, an investigational hypoxia-inducible factor prolyl hydroxylase inhibitor. Additionally, analyses of the efficacy endpoints from the roxadustat Phase III OLYMPUS and ROCKIES trials for anemia in CKD-NDD or CKD-DD patients, respectively, will be included in oral presentations.

Joris Silon, Senior Vice President, CVRM, BioPharmaceuticals Business Unit, said: "The unprecedented number of abstracts being presented by AstraZeneca at ASN 2019 demonstrates our commitment to advancing the care of chronic kidney disease and its complications, which affect millions of patients worldwide. We are applying our clinical and medical expertise in cardiovascular, renal and metabolism to generate new insights in chronic kidney disease that will make a real difference to patients."

At the meeting, AstraZeneca will also present analyses from the landmark Phase III DAPA-HF trial, the first outcomes trial with a SGLT2 inhibitor assessing the treatment of heart failure in patients with reduced ejection fraction, with and without type-2 diabetes (T2D). Additional data from the Phase III DECLARE-TIMI 58 trial will also be presented, showing the effect of FARXIGA on renal disease progression in patients with T2D.

For LOKELMA (sodium zirconium cyclosilicate), a post-hoc analysis evaluating potassium balance from the Phase IIIb DIALIZE trial will show efficacy and safety data of the medicine in patients with hyperkalemia on hemodialysis.

Notable AstraZeneca abstracts at ASN 2019 include:

For a complete list of AstraZeneca data presentations during Kidney Week 2019, please access the ASN website.

Indication and Limitations of Use for FARXIGA^® (dapagliflozin) tablets

FARXIGA is indicated:

• as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
• to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular disease or multiple cardiovascular risk factors

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

Important Safety Information for FARXIGA^® (dapagliflozin) tablets

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: FARXIGA causes intravascular volume contraction and can cause acute kidney injury. Reports of acute kidney injury requiring hospitalization and dialysis have occurred with FARXIGA. If acute kidney injury occurs, discontinue and promptly treat

Increases in serum creatinine and decreases in eGFR may be observed with initiation of FARXIGA. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses

Before initiating FARXIGA, evaluate renal function and monitor periodically. FARXIGA is not recommended when the eGFR is <45 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
• Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): Rare but serious, life-threatening cases have been reported in patients receiving SGLT2 inhibitors including FARXIGA. Cases have been reported in females and males. Serious outcomes have included hospitalization, surgeries, and death. Assess patients presenting with pain or tenderness, erythema, swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue FARXIGA
• Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately

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.

Please see accompanying US Full Prescribing Information and Medication Guide for FARXIGA.

IMPORTANT SAFETY INFORMATION FOR LOKELMAtm (sodium zirconium cyclosilicate) 10 g FOR ORAL SUSPENSION

WARNINGS AND PRECAUTIONS:

• Gastrointestinal Adverse Events in Patients with Motility Disorders: Avoid LOKELMA in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders. LOKELMA has not been studied in patients with these conditions and it may be ineffective and may worsen gastrointestinal conditions

• Edema: Each 5 g dose of LOKELMA contains approximately 400 mg of sodium. In clinical trials of LOKELMA, edema was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (eg., heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate. Increase the dose of diuretics as needed

ADVERSE REACTIONS: The most common adverse reaction with LOKELMA was mild to moderate edema. In placebo-controlled trials up to 28 days, edema was reported in 4.4%, 5.9%, 16.1% of patients treated with 5 g, 10 g and 15 g of LOKELMA once daily, respectively vs 2.4% of patients receiving placebo.

DRUG INTERACTIONS: LOKELMA can transiently increase gastric pH. In general, oral medications with pH-dependent solubility should be administered at least 2 hours before or 2 hours after LOKELMA. Spacing is not needed if it has been determined the concomitant medication does not exhibit pH-dependent solubility.

INDICATION AND LIMITATION OF USE
LOKELMA is indicated for the treatment of hyperkalemia in adults.

LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

PLEASE READ FULL PRESCRIBING INFORMATION.

About AstraZeneca in CVRM
Cardiovascular, Renal & Metabolism (CVRM) together forms one of AstraZeneca's three therapy areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company's ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular 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 therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. 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.