20 October 2020 07:00 BST
For roxadustat, more than 40 abstracts present safety and efficacy outcomes in anaemia of chronic kidney disease
For Farxiga, new subgroup data from the DAPA-CKD Phase III trial assesses the potential benefit irrespective of the cause of chronic kidney disease
Data demonstrate progress towards helping prevent or slow the progression of chronic kidney disease and address life-threatening complications
AstraZeneca will present 84 abstracts, including 12 oral presentations and three late-breaking abstracts, across its industry-leading renal portfolio which includes roxadustat, Farxiga (dapagliflozin) and Lokelma (sodium zirconium cyclosilicate), at ASN Kidney Week 2020 Reimagined, taking place virtually from 22-25 October 2020.
The data advance AstraZeneca’s ambition to create a coordinated pathway for renal patients to advance earlier diagnosis and help prevent or slow the progression of chronic kidney disease (CKD) and address its life-threatening complications, such as anaemia and hyperkalaemia.1,2
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “The breadth of data being presented by AstraZeneca demonstrates the growing momentum of our renal portfolio. Our ambition is to provide new treatments for hundreds of millions of patients with chronic kidney disease, a progressive condition for which there currently is no cure. We are particularly excited to share insights into the safety and efficacy of roxadustat in anaemia of chronic kidney disease and new subgroup data from the DAPA-CKD trial looking at the benefit of Farxiga regardless of disease cause.”
Roxadustat - redefining the management of anaemia of CKD
More than 40 abstracts will be presented on roxadustat, a first-in-class oral hypoxia-inducible-factor prolyl hydroxylase inhibitor (HIF-PHI). The abstracts provide new insights on the potential of the medicine to transform the standard of care in anaemia of CKD across key patient sub-populations, notably:
- Late-breaking presentations of pooled analyses of Phase III trials investigating the association between haemoglobin levels and CV outcomes in dialysis-dependent (DD) and non-dialysis dependent (NDD)-CKD patients. Cardiovascular (CV) outcomes are common and serious complications in patients with CKD.3-5
- An oral presentation exploring whether roxadustat can reduce the risk of hospitalisation for heart failure, a common comorbidity in patients with CKD.6
- Analyses of whether roxadustat has the potential to reduce the risk of red blood cell (RBC) transfusions, a treatment for anaemia associated with additional complications, in both DD-CKD and NDD-CKD patients.7
- An analysis exploring the effect of roxadustat on achieving haemoglobin levels ≥10 g/dL in patients with NDD-CKD.8
- New data from pooled analyses of Phase III trials on DD-CKD patient subgroups, including those who are receiving peritoneal dialysis and are new to dialysis.9,10
Farxiga - setting a new standard in early CKD protection
New late-breaking subgroup data from the ground-breaking DAPA-CKD Phase III trial evaluating the potential benefit of Farxiga in patients with CKD irrespective of the underlying cause.11 Detailed results presented in August and published in The New England Journal of Medicine established Farxiga as the first medicine to significantly prolong survival in a renal outcomes trial in patients with CKD with and without type-2 diabetes (T2D).
Lokelma - advancing proactive potassium management
New sub-analyses of the DIALIZE Phase IIIb trial and real-world evidence in patients living with CKD and hyperkalaemia demonstrate the potential of Lokelma as an option for hyperkalaemia management.12-14 Hyperkalaemia is a common complication in patients with CKD and can result in serious arrhythmias, sudden cardiac arrest, paralysis and weakness, and even death.2,15,16 If not managed effectively, complications like hyperkalaemia can impact ongoing treatment approaches, leading to life-saving treatments being reduced or discontinued.16
Uncovering the unique unmet needs of the CKD patient community
AstraZeneca will also present new insights into patients’ experiences living with CKD as well as actionable gaps in treatment and management. New data will be presented from DISCOVER-CKD, a trial that assesses current real-world practice patterns and clinical management of patients with CKD. It reveals the burden of disease and factors that determine poor clinical outcomes, underscoring the need for improved treatment options.17
AstraZeneca key abstracts at ASN Kidney Week 2020 include:
ASN Kidney Week 2020 abstracts are available online.
Roxadustat is a first-in-class oral small molecule hypoxia-inducible-factor prolyl hydroxylase inhibitor (HIF-PHI) that promotes erythropoiesis through increased endogenous production of erythropoietin; improved iron absorption, transport and mobilisation; and downregulation of hepcidin, which helps to overcome the negative impact of inflammation on haemoglobin synthesis and red blood cell production. Roxadustat is approved in China for the treatment of anaemia in adult patients with CKD, both on dialysis and not on dialysis. In Japan, roxadustat is approved for the treatment of anaemia in CKD patients on dialysis, and a supplemental New Drug Application (NDA) for the treatment of anaemia in CKD patients not on dialysis is under regulatory review. The roxadustat NDA for the treatment of anaemia in CKD in both NDD and DD is under review by the US Food and Drug Administration with a decision expected in Q4 2020. The Marketing Authorisation Application for roxadustat for the treatment of anaemia in CKD in both NDD and DD was filed by Astellas and accepted by the European Medicines Agency for review on 21 May 2020. Roxadustat is also in clinical development for anaemia associated with myelodysplastic syndromes (MDS) and for chemotherapy-induced anaemia (CIA).
AstraZeneca and FibroGen Inc. (FibroGen) are collaborating on the development and commercialisation of roxadustat for the potential treatment of anaemia in the US, China and other markets in the Americas and in Australia/New Zealand, as well as Southeast Asia. Astellas and FibroGen are collaborating on the development and commercialisation of roxadustat for the potential treatment of anaemia in territories including Japan, Europe, the Commonwealth of Independent States, the Middle East and South Africa. At ASN Kidney Week 2020 Reimagined, roxadustat data will be sponsored and presented by Astellas, AstraZeneca and FibroGen.
Farxiga (dapagliflozin) is a first-in-class, oral, once-daily sodium-glucose co-transporter-2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monotherapy and as part of combination therapy as an adjunct to diet and exercise to improve glycaemic control, with the additional benefits of weight loss and blood-pressure reduction. In the DECLARE CV outcomes trial in adults with T2D, Farxiga reduced the risk of the composite endpoint of hospitalisation for heart failure (hHF) or CV death versus placebo, when added to standard of care.
In May 2020, Farxiga was approved in the US to reduce the risk of CV death and hHF in adults with heart failure (HF) (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D. In the DAPA-CKD Phase III trial in patients with CKD, Farxiga met all primary and secondary endpoints, providing overwhelming efficacy. Farxiga is currently being tested for patients with HF in the DELIVER (HF with preserved ejection fraction, HFpEF) and DETERMINE (HFrEF and HFpEF) trials. Farxiga will also be tested in patients without T2D following an acute myocardial infarction (MI) or heart attack in the DAPA-MI trial – a first of its kind, indication-seeking registry-based randomised controlled trial. Farxiga has a robust programme of clinical trials that includes more than 35 completed and ongoing Phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience.
Lokelma (sodium zirconium cyclosilicate) is an insoluble, non-absorbed sodium zirconium silicate, formulated as a powder for oral suspension, that acts as a highly selective potassium-removing medicine. It is administered orally, is odourless, tasteless and stable at room temperature. It has been studied in three double-blind, placebo-controlled trials and one 12-month open-label clinical trial in patients with hyperkalaemia.
AstraZeneca in CVRM
Cardiovascular, Renal and 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 comorbidities. 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.
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
1. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis 2006; 47(5 Suppl 3):S1-146.
2. National Kidney Foundation. Clinical Update on Hyperkalemia: A chronic Risk for CKD Patients and a Potential Barrier to Recommended CKD Treatment. New York: National Kidney Foundation; 2014 [cited 16 October 2020]. Available from: URL: https://www.kidney.org/sites/default/files/02-10-6785_HBE_Hyperkalemia_Bulletin.pdf.
3. Fishbane S et al. Associations between Achieved Hemoglobin and Cardiovascular Outcomes in the Pooled Phase 3 Trials of Roxadustat in Dialysis-dependent Patients with Anemia of Chronic Kidney Disease. Abstract #PO2625 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
4. Provenzano R et al. Associations between Achieved Hemoglobin and Cardiovascular Outcomes in Phase 3 Roxadustat Studies of Non dialysis-dependent Patients with Anemia of Chronic Kidney Disease. Abstract # #PO2626 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
5. Centers for Disease Control and Prevention (CDC). Chronic Kidney Disease: Common - Serious - Costly; 12 December 2019 [cited 16 October 2020]. Available from: URL: https://www.cdc.gov/kidneydisease/prevention-risk/CKD-common-serious-costly.html.
6. Provenzano R et al. Pooled Analyses of the Phase 3 Roxadustat Studies: Congestive Heart Failure Hospitalization Rates in Dialysis and Non-Dialysis Patients with Anemia treated with Roxadustat versus Comparators. Abstract #SA-OR39 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
7. Fishbane S et al. Roxadustat Lowers Risk of RBC Transfusion in Patients with Anemia in CKD. Abstract #PO0256 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
8. Rastogi, A et al. Roxadustat treatment corrects anemia to hemoglobin (Hb) values ≥10 g/dL in the majority of patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Abstract #PO0264 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
9. Chan, TM et al. Efficacy and Safety of Roxadustat in Patients with Dialysis-dependent Chronic Kidney Disease and Anemia on Peritoneal Dialysis. Oral #SU-OR24 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
10. Provenzano R et al. Subgroup Analyses of Efficacy of Roxadustat for Treatment of Anemia in Patients with Incident–Dialysis-dependent Chronic Kidney Disease Abstract #PO0259 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
11. Wheeler D. Effects of dapagliflozin on kidney function, cardiovascular events and all-cause mortality according to cause of kidney disease in the DAPA-CKD trial. Abstract #FR-OR58 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
12. Fishbane S. Risk of Hypokalemia in Hyperkalemic Hemodialysis Patients. Abstract #PO1051 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
13. Tafesse E, James G, Sugrue D, Hurst M, Hoskin L, Badora K, McEwan P. The relationship between comorbidities and hyperkalaemia in patients with chronic kidney disease. Abstract #PO1448 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
14. Tafesse E, James G, Hurst M, Hoskin L, Badora K, Sugrue D, McEwan P. The relationship between chronic kidney disease duration, serum potassium level and adverse outcomes. Abstract #PO1450 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
15. American Heart Association. Part 10.1: Life-Threatening Electrolyte Abnormalities. Circulation 2005; 112(24_suppl):IV-121-IV-125.
16. Montford JR et al. How Dangerous is Hyperkalaemia? J Am Soc Nephrol. 2017 Nov;28(11):3155-3165.
17. U.S. National Institutes of Health. A Study on Patients With Chronic Kidney Disease (CKD) to Assess Treatment Experience and Patterns, Effect of the Treatment, Patient Outcomes and Patient Quality of Life (DISCOVER CKD) [Identifier: NCT04034992] [cited 16 October 2020]. Available from: URL: https://clinicaltrials.gov/ct2/show/NCT04034992.