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 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.
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Key abstracts |
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Presentation/poster details |
LOKELMA |
Sodium zirconium cyclosilicate for hyperkalemia: results of the
randomized, placebo-controlled, multi-dose HARMONIZE-GLOBAL study |
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Poster #TH-PO1158
Thursday, Oct 25, 10:00 AM to 12:00 PM
Poster session: Late-Breaking Clinical Trials Posters [LB-PO]
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Correction of serum potassium with sodium zirconium cyclosilicate in
Japanese patients with hyperkalemia: a dose-finding study |
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Poster #TH-PO1157
Thursday, Oct 25, 10:00 AM to 12:00 PM
Poster session: Late-Breaking Clinical Trials Posters [LB-PO]
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Real-world dosing practices of renin-angiotensin-aldosterone system
inhibitors are associated with risk of adverse clinical events in CKD patients |
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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]
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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).1
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Key abstracts |
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Presentation/poster details |
Anemia in CKD |
Anemia treatment patterns in chronic kidney disease: results from
three international surveys among physicians |
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Poster #TH-PO249
Thursday, Oct 25, 10:00 AM to 12:00 PM
Session Title: Anemia and Iron Metabolism: Clinical [PO0202-1]
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Associations of hemoglobin levels and quality of life in patients with
chronic kidney disease: pooled results from three international surveys |
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Poster #TH-PO250
Thursday, Oct 25, 10:00 AM to 12:00 PM
Session Title: Anemia and Iron Metabolism: Clinical [PO0202-1]
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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.
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Key abstracts |
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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 |
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Poster #TH-PO1156
Thursday, Oct 25, 10:00 AM to 12:00 PM
Session Title: Late-Breaking Clinical Trials Posters [LB-PO]
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Reduction in albuminuria with dapagliflozin cannot be predicted by
baseline clinical characteristics or changes in most other risk markers |
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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]
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Early Science |
APOL1 antisense oligonucleotide treatment ameliorates IFN?-induced
proteinuria in genomic APOL1 transgenic mice |
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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]
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Single Cell RNA-Seq identifies molecular fingerprints of endothelial
cell subpopulations in kidney |
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Poster #FR-PO942
Friday, Oct 26, 10:00 AM to 12:00 PM
Session Title: Development, Stem Cells, Regenerative Medicine - II [PO0501-2]
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The distribution profile of anti-sense oligonucleotides indicates that
proximal tubular targets should be prioritized in renal disease |
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Poster #SA-PO631
Saturday, Oct 27, 10:00 AM to 12:00 PM
Session Title: Pharmacology [PO1700-1]
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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.2,3,4
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.5,6 Anemia is associated with increased risk
of hospitalization, cardiovascular complications and death.5,6 In addition, anemia frequently causes significant
fatigue, cognitive dysfunction, and decreased quality of life.7,8 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.
References
- Jackson, J., van Haalen, H., Salehi, H., Milligan, G., Moon, R. Anemia Treatment Patterns in Chronic
Kidney Disease: Results From Three International Surveys Among Physicians [abstract]. American Society of Nephrology; 2018 Oct
26; San Diego; Abstract nr TH-PO249.
https://www.asn-online.org/education/kidneyweek/2018/program-abstract.aspx?controlId=3023640.
- Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium
lowering for 28 days among outpatients with hyperkalemia. JAMA. 2014. doi:10.1001/jama.2014.15688.
- Kovesdy CP. Management of hyperkalemia in chronic kidney disease. Nat Rev Nephrol. 2014.
doi:10.1038/nrneph.2014.168.
- Vardeny O, et al. Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients
with severe heart failure treated with a mineralocorticoid receptor antagonist. Circ Heart Fail. 2014;7: 573–579.
- National Kidney Foundation. “Managing Anaemia When You Have Kidney Disease or Kidney Failure.”
2014.
- National Institute of Diabetes and Digestive and Kidney Diseases. “Anaemia in Chronic Kidney
Disease.” 2014.
- KDOQI Clinial Practice Guidelines and Clinical Practice Recommendations for Anaemia in Chronic Kidney
Disease. Am J Kidney Dis. 2006 May;47(5):S1-S132
- American Heart Association. “Life-Threatening Electrolyte Abnormalities.” 2005; Circulation.
2005;112:IV-121-IV-125.
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