AstraZeneca to present new data demonstrating breadth of research portfolio in renal disease at ASN kidney week 2018

35 scientific data presentations and publications, including new evidence for LOKELMA (sodium zirconium cyclosilicate) in hyperkalemia and FARXIGA® (dapagliflozin) on renal endpoints in type-1 diabetes

Latest data on potential new medicine roxadustat for anemia in chronic kidney disease and early-stage findings from multiple investigational treatments

AstraZeneca (NYSE: AZN) will present new research spanning the Company’s Cardiovascular, Renal and Metabolism (CVRM) therapy area at the American Society of Nephrology (ASN) Kidney Week Annual Meeting in San Diego, US, October 23-28, 2018.

ASN Kidney Week is a landmark meeting for AstraZeneca, which will provide new and in-depth research aiming to inform clinical practice across the renal treatment paradigm, while also advancing science that uncovers commonalities and potential treatment targets across cardiovascular, renal and metabolic diseases.

Danilo Verge, Vice President, Cardiovascular, Renal and Metabolism, Global Medical Affairs at AstraZeneca said: “The data we are presenting at ASN Kidney Week demonstrate our ambition to advance treatment for patients with chronic kidney disease and its associated complications. We are exploring solutions to help address unmet medical need, including disease modification during early-stage diagnosis to managing potentially life-threatening complications as patients progress to dialysis and end-stage renal disease.”

New research will include data from the Phase III HARMONIZE Global trial to evaluate the safety and efficacy of LOKELMA™ for the treatment of patients with hyperkalemia in Japan, Russia, Korea and Taiwan. These findings add to the growing body of evidence for LOKELMA and will support regulatory filings in those markets.

In the US, LOKELMA was approved by the Food and Drug Administration (FDA) in May 2018 for the treatment of hyperkalemia in adults.

Building awareness of clinical practice with real-world evidence and clinical data
AstraZeneca will present and publish 11 abstracts that focus on the treatment and management of hyperkalemia, including an analysis of real-world dosing practices of renin-angiotensin-aldosterone system (RAAS) inhibitors and their association with risk of adverse clinical events in patients with chronic kidney disease (CKD).

The risk of hyperkalemia–a serious condition characterized by abnormally high levels of potassium in the blood associated with cardiovascular, renal and metabolic diseases–increases significantly for patients with CKD and those on common medications for heart failure (HF), such as RAAS inhibitors which can increase potassium in the blood.

Key abstracts

Presentation/poster details

LOKELMA

Sodium zirconium cyclosilicate for hyperkalemia: results of the randomized, placebo-controlled, multi-dose HARMONIZE-GLOBAL study

Poster #TH-PO1158

Thursday, Oct 25, 10:00 AM to 12:00 PM

Poster session: Late-Breaking Clinical Trials Posters [LB-PO]

Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a dose-finding study

Poster #TH-PO1157

Thursday, Oct 25, 10:00 AM to 12:00 PM

Poster session: Late-Breaking Clinical Trials Posters [LB-PO]

Real-world dosing practices of renin-angiotensin-aldosterone system inhibitors are associated with risk of adverse clinical events in CKD patients

Abstract #FR-OR116

Room 26A

Friday, Oct 26, 5:18 PM to 5:30 PM

Session Title: Towards Better Medication Usage in Patients with CKD [OR1902-1]

Evaluating unmet needs in anemia management for CKD patients
AstraZeneca will provide new data on investigational medicine roxadustat, as well as additional research on the treatment paradigm of anemia and CKD patients. Roxadustat is a potential first-in-class new medicine and orally administered small molecule currently in Phase III development for anemia associated with CKD in dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients.

Data from large registries around the globe, including US, China and countries in Europe, indicate a strong association between anemia and poor quality of life, though many NDD patients with anemia remain untreated due to concerns with the safety of the current standard of care, erythropoiesis stimulating agents (ESAs).

Key abstracts

Presentation/poster details

Anemia in CKD

Anemia treatment patterns in chronic kidney disease: results from three international surveys among physicians

Poster #TH-PO249

Thursday, Oct 25, 10:00 AM to 12:00 PM

Session Title: Anemia and Iron Metabolism: Clinical [PO0202-1]

Associations of hemoglobin levels and quality of life in patients with chronic kidney disease: pooled results from three international surveys

Poster #TH-PO250

Thursday, Oct 25, 10:00 AM to 12:00 PM

Session Title: Anemia and Iron Metabolism: Clinical [PO0202-1]

Early science and investigational combination treatments
Delving deep into the science and molecular basis of CVRM diseases, AstraZeneca’s Innovative Medicines and Early Development (IMED) Biotech Unit will present eight abstracts focusing on mechanisms of obesity, HF and renal disease.

New modalities provide an opportunity to design therapeutics for disease mechanisms previously considered difficult to address, and are a key part of our early science strategy. Our research, in collaboration with Ionis Pharmaceuticals, on antisense oligonucleotides (ASO) as a potential modality for new targets in CKD will be an oral presentation, with an additional poster that furthers our understanding of the science behind this new modality. An additional key abstract investigates distinct endothelial cell subpopulations using cutting-edge single cell RNA-sequencing analysis.

Early scientific data on verinurad, an investigational treatment for uric acid elimination, will be presented. Expanding on our existing portfolio, a poster presentation will describe the investigation of dapagliflozin on serum uric acid when given in combination with verinurad and febuxostat. Dapagliflozin is indicated to improve glycemic control in type 2 diabetes. It is not indicated for type 1 diabetes, reduction in serum uric acid or albuminuria.

Key abstracts

Presentation/poster details

Dapagliflozin

Effect of adding dapagliflozin as an adjunct to insulin on urinary albumin to creatinine ratio over 52 weeks in adults with type 1 diabetes

Poster #TH-PO1156

Thursday, Oct 25, 10:00 AM to 12:00 PM

Session Title: Late-Breaking Clinical Trials Posters [LB-PO]

Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers

Abstract #SA-OR081

Room 1B

Saturday, Oct 27, 5:06 PM to 5:18 PM

Session Title: New Considerations for Renoprotection Clinical Trials [OR1902-2]

Early Science

APOL1 antisense oligonucleotide treatment ameliorates IFNγ-induced proteinuria in genomic APOL1 transgenic mice

Abstract #FR-OR068

Room 33C

Friday, Oct 26, 4:30 PM to 4:42 PM

Session Title: Genetics and Kidney Diseases: Beyond PKD [OR1002-1]

Single Cell RNA-Seq identifies molecular fingerprints of endothelial cell subpopulations in kidney

Poster #FR-PO942

Friday, Oct 26, 10:00 AM to 12:00 PM

Session Title: Development, Stem Cells, Regenerative Medicine - II [PO0501-2]

The distribution profile of anti-sense oligonucleotides indicates that proximal tubular targets should be prioritized in renal disease

Poster #SA-PO631

Saturday, Oct 27, 10:00 AM to 12:00 PM

Session Title: Pharmacology [PO1700-1] 

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

INDICATION AND LIMITATION OF USE FOR LOKELMA™ (sodium zirconium cyclosilicate) 10 g ORAL SUSPENSION
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.

IMPORTANT SAFETY INFORMATION

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.

PLEASE READ FULL PRESCRIBING INFORMATION For LOKELMA.

INDICATION AND LIMITATIONS OF USE FOR FARXIGA® (dapagliflozin) tablets 5 mg and 10 mg

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

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 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

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

Please read US Full Prescribing Information and Medication Guide for FARXIGA

NOTES TO EDITORS

About Hyperkalemia
The risk of hyperkalemia is associated with common comorbidities including chronic kidney disease, HF and diabetes, and these are the same conditions in which RAAS inhibitors are recommended in guidelines. To help prevent the recurrence of hyperkalemia, important guideline-recommended RAAS inhibitor therapy is often modified or discontinued. Hyperkalemia may affect 40% to 50% of patients with CKD, and up to 50% of chronic heart failure (CHF) patients on RAAS inhibitors.

About Anemia in CKD
Anemia is a serious medical condition in which patients have insufficient red blood cells and low levels of hemoglobin (“Hb”), a protein in red blood cells that carries oxygen to cells throughout the body. Anemia is associated with increased risk of hospitalization, cardiovascular complications and death. In addition, anemia frequently causes significant fatigue, cognitive dysfunction, and decreased quality of life. Severe anemia is common in patients with CKD and other serious illnesses. Even when it accompanies prevalent and serious diseases, anemia is often not effectively treated.

Anemia is particularly prevalent in patients with CKD, which itself affects more than 200 million people worldwide and is generally a progressive disease characterized by gradual loss of kidney function that may eventually lead to kidney failure.

According to the United States Renal Data System, a majority of dialysis-eligible CKD patients in the US are currently on dialysis. Of the approximately 475,000 patients receiving dialysis in the US, around 83% are being treated with ESAs for anemia. In clinical practice, patients typically do not receive ESA treatment for their anemia until they initiate dialysis.

About AstraZeneca in Cardiovascular, Renal & Metabolism (CVRM)
Cardiovascular, renal and metabolism together form one of AstraZeneca’s main therapy areas and 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. Our 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 main therapy areas - Oncology, Cardiovascular, Renal & Metabolism 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.

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US-24305  Last Updated 10/18