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Roxadustat is under regulatory review for the treatment of anemia of chronic kidney disease (CKD). Anna Reznichenko, Principal Scientist, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, has devised a novel method based on market segmentation analysis for handling massive datasets drawn from the financial industry. AstraZeneca will also present new insights into patientsâ experiences living with CKD as well as actionable gaps in treatment and management. A 3D model with the vascular and tubular aspects of the kidney to emulate cell cross-talk in different organ compartments is the goal that until now may have seemed beyond scientists’ reach. Creating realistic, living components of a healthy kidney will be a vital tool for understanding kidney function. In the age of ‘omics and data processing, we believe we have reached a turning point. Published in the New England Journal of Medicine, the study is based on the results of exome sequencing more than 3,300 patients. While there are currently available treatments that benefit patients with CKD, there are no treatments that specifically target the ⦠3D bioprinting involves printing-like techniques, where fugitive ‘ink’ is printed onto a gelatin/fibrogen matrix to pattern open vascular and tubular channels. New data will be presented from DISCOVER-CKD, a trial that assesses current real-world practice patterns and clinical management of patients with CKD. In addition to the increasing prevalence and limited treatment options, CKD is known as a ‘disease multiplier’. Many individuals with these diseases have either symptoms or underlying pathologies associated with more than one of these diseases, so treating them collaboratively is essential. Patients were aged â¥18 years, with â¥1 UACR measure and two measures of eGFR 0 ⦠The current symptom-based approach ignores the different underlying molecular causes of disease and leaves potential for misdiagnosis. The study is also using mobile technology to allow patients to provide their own experiences with CKD and improve patient dialogue as well as assess AZ’s specific outcomes via prospective data collection. We are now looking to identify urinary biomarkers which could be used to reveal patients’ molecular disease classes non-invasively, allowing us greater precision when allocating the right patients to the right trials and in the future, potentially provide tailored treatments based on scientifically-determined individual disease categories. We have two postdoctorate fellows focused on this project – the first aims to create a completely new type of chip with a three-cell-type culture, and the second will use an established chip to try to reconstitute the subtleties of chronic human disease in a way that could never have been done in vitro, by fine tuning factors like flow rates and shear stresses. Our ambitions are high: we want to stop disease progression, manage morbidity and mortality, and ultimately modify and even reverse the disease itself. T: +44 (0)20 7240 6999 The current analysis examined data from US-based Limited ⦠We are excited to partner with AstraZeneca to increase the complexity and utility of our 3D kidney tissue models – bioprinting enables us to rapidly design and fabricate a wide range of vascularised human tissues. Organs-on-Chips technology is a game changer for scientists at AstraZeneca: these micro-engineered systems model the in vivo micro-environment, and represent a new paradigm for cell-based models. AstraZeneca and BenevolentAI today began a long-term collaboration to use artificial intelligence (AI) and machine learning for the discovery and development of new treatments for chronic kidney disease (CKD⦠Read more. For a disease with many different underlying causes that produce the same symptoms, a molecular approach to diagnosis is a logical step and is essential if we are to develop effective, patient-specific treatments. However, access to the data itself is only part of the picture: the next step is analysing the patterns within the data points. We have, for years, been investigating cells in isolation in a dish. Little Bookham DISCOVER CKD is an international observational cohort study in patients with CKD, comprising both prospective and retrospective patient cohorts. The study included patients aged >18 years (>20 JMDV) with a diagnostic CKD ⦠At AstraZeneca, we are dedicated to changing the future for CKD patients. We are investigating the drivers of disease and progression of CKD using a rigorous, science-led approach and adopting techniques that aim to break new ground in research. The DISCOVER CKD study is characterising contemporary real-world management of CKD, to provides insights into the current gaps in treatment and management of CKD⦠Modelling this interplay, which would take place in a real, living kidney is crucial for the creation of a realistic, relevant model system. While there are currently available treatments that benefit patients with CKD, there are no treatments that specifically target the cause of CKD. Anaemia in NDD patients with CKD is frequent and largely undertreated, and rescue therapies including blood transfusions are more often used as first-line treatments than preventative therapies such as intravenous iron or erythropoiesis-stimulating agents. Until now, cell-based models that have been used for compound testing have not been able to reflect the complexity of the kidney environment and results would not always be a faithful representation of what happens in the body. ASOs can be designed to bind to almost any defined genetic sequences, meaning they have potential for use in diseases with genetic origin. Imagine how much more information we will get from this system. The DISCOVER CKD study is characterising contemporary real-world management of CKD, to provides insights into the current gaps in treatment and management of CKD, as well as care pathways and novel endpoints. However, exome sequencing – the analysis of the protein coding regions of the genome – could change this. According to the pharma company, Farxiga (dapagliflozin) is the first therapy shown to significantly prolong patient survival in CKD ⦠It is concerning that we have this on an epidemic scale. To use this new knowledge to our best advantage, we need the right research tools to simulate the disease and test our hypotheses. AstraZeneca will present a series of sub-analyses from the Lokelma Phase IIIb DIALIZE trial reinforcing the effectiveness of this medicine to manage hyperkalaemia in patients with CKD on ⦠Using data from the Renal Pre-competitive Consortium (RPC2) – a unique partnership of industrial and academic collaborators – gives Anna access to the largest-ever patient sample bank for renal transcriptomics (analysis of gene expression in kidney biopsies), containing over 250 genome-wide expression profiled samples, with data from patients at all stages of disease. The DISCOVER CKD study population for all countries except Japan includes male and female patients with CKD aged 18 years or over. DISCOVER-CKD encompasses large retrospective electronic medical records (EMRs) and claims data between 2008 and 2020. The results from the Phase III DPA-CKD trial showed promising results in patients with chronic kidney disease (CKD), AstraZeneca has reported. With these groundbreaking techniques, we can test compound behaviour and hope to shed new light on previously elusive disease mechanisms. People living with CKD progressively lose kidney function, but may not know they even have the disease until the later stages. We are looking to a future where we can identify drugs that target the root cause of disease and recruit patients with specific genotypes to the right trials. Scientific advances have increased our understanding of the links between cardiovascular, renal and metabolic diseases. The complexity of the kidney means it has been virtually impossible to emulate in classical in vitro systems, while in vivo models are resource intensive to produce, and not always translatable to human systems. Mansard House At AstraZeneca, our CaReMe approach is to see and embrace the full cardio-renal and metabolic picture and use this knowledge to redefine the way these diseases are understood and treated. We encourage you to read the privacy policy of every website you visit. LONDON, Jan. 27, 2021 /PRNewswire/ -- BenevolentAI today announced that the biopharmaceutical company AstraZeneca has selected a novel chronic kidney disease (CKD) target ⦠This platform allows us to explore drug candidates that specifically address disease targets, many of which cannot be treated by traditional drug types. The ultimate aim will be to try to induce disease conditions and then treat them. We describe treatment pathways of key medications prescribed to CKD patients in DISCOVER CKD. We are investing in the development of new, sophisticated models that mimic the human kidney more accurately than has ever previously been possible. By focusing on early disease detection underpinned by precision medicine, we hope that in the future patients will be matched with treatments most likely to work for them. We also need an equivalent standard for understanding the experiences of patients in the real world,” said Joris Silon, senior vice president for cardiovascular, renal and metabolism at AZ. LONDON, Jan. 27, 2021 /PRNewswire/ -- BenevolentAI today announced that the biopharmaceutical company AstraZeneca has selected a novel chronic kidney disease (CKD) ⦠When we put two cell types together, we suddenly see that they behave differently – one cell influences the results from the other. With organ on a chip technology we can go even further than this and add conditions such as flow and shear stress, mimicking the conditions in the kidney even further. Observing a complete system enables a better understanding of kidney function – and dysfunction. You have selected a link that will take you to a site maintained by a third party who is solely responsible for its contents. Please refer to your approved national product label (SmPC) for current product information. AstraZeneca presented new findings from the DISCOVER Chronic Kidney Disease (CKD) study at the American Society of Nephrologists (ASN) Kidney Week 2020 Congress last week. These data enhance our disease understanding, as well as suggesting that genetic diagnosis can now be used in patients with previously unknown causes of the disease, and highlights the potential of early genetic testing to accurately identify and target patient subpopulations towards relevant clinical trials and targeted therapies. Distinct, homogeneous patient categories can be most effectively revealed using a dataset of this size. The new model systems we are embedding into our research pipeline to bridge this gap include 3D bioprinting and organs-on-chips. Sometimes I look around the room when we have big meetings and consider that every tenth person in the room will have kidney disease. Our country sites can be located in the AZ Network. We describe patient characteristics and the prevalence of CKD according to the 2012 KDIGO categories in patients with CKD. Leatherhead The study does not attempt to test any ⦠In the initial key findings, AZ found that over 600,000 patients with non-dialysis-dependent-CKD (NDD-CKD) have been identified in the study cohort which aims to describe baseline characteristics of an NDD-CKD population with and without anaemia. Chronic kidney disease (CKD) is a common and debilitating condition that affects around 1 in 10 people worldwide,1 and the prevalence is increasing. New data will be presented from DISCOVER-CKD, ⦠In partnership with Ionis Pharmaceuticals, we are researching APOL-1 – a gene with variants that is related to an increased risk of early onset kidney disease and rapid progression. The flow represents the flow of blood carrying nutrients, takes away waste products, and also creates mechanical forces, all critical factors for the functioning of the kidney. The international hybrid observational cohort study, undertaken in collaboration with a scientific committee, includes both prospective and retrospective cohorts of patient with CKD. AstraZeneca provides this link as a service to website visitors. Any reference in these archives to AstraZeneca products or their uses may not reflect current medical knowledge and should not be used as a source of information on the present product label, efficacy data or safety data. We are in a stronger position than ever before to look for targets and treatments now we have a deeper molecular understanding of CKD. AstraZeneca biopharmaceuticals R&D executive vice president Mene Pangalos said: âThere is a serious, unmet need for better and earlier treatment options for patients with chronic kidney disease. Patients were aged â¥18 years, with â¥1 UACR ⦠Animal models go some way towards addressing this; although even mammalian systems can lack translatability to human systems, especially with compounds that show species differences in metabolism and toxicity. Surrey KT23 3JG, E: editorial@pharmatimes.com © Copyright PharmaTimes Media Limited 2021, International Clinical Researcher of the Year, Clinical Researcher of the Year - The Americas, Gilead’s HIV therapy Biktarvy demonstrates long-term sustained efficacy, Antibiotic Research UK calls for clear guidance on the use of antibiotics and COVID-19 vaccines, Novartis’ canakinumab fails to improve overall survival in lung cancer trial, NHS England agrees deal with Novartis for access to SMA gene therapy Zolgensma, New real-world evidence for Pfizer/BioNTech COVID-19 vaccine, NICE rejects AZ’s Lynparza for metastatic prostate cancer, UK Marketing Specialist - Wound Care - Home Based, Clinical Research Nurse - Respiratory Vaccine Study - Oxford. This cohort’s size provides information into a highly comorbid population with conditions including hypertension, heart failure, stroke and type 2 diabetes. The DISCOVER CKD retrospective cohort was extracted using the US TriNetX hospital-EMR and Japan Medical Data Vision (JMDV) databases. Julie Williams believes that one reason for the limited number of treatment options for kidney patients is strongly linked to the lack of translatable systems as there is a high attrition rate with kidney candidate drugs in clinical trials. One emerging treatment strategy is to target protein expression using antisense oligonucleotides (ASOs). Principal Scientist, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, Senior Vice President, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, Head of the Centre for Genomics Research, Discovery Sciences, R&D, Senior Director, Bioscience CKD, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, Director, Bioscience CKD, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, Chief Operating Officer, Ionis Pharmaceuticals, Senior Project Leader, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, https://www.kidneycareuk.org/news-and-campaigns/news/estimated-1-10-people-worldwide-have-chronic-kidney-disease/, https://www.sciencedirect.com/science/article/pii/S0914508710001802, https://www.kidney-international.org/article/S0085-2538(17)30095-9/pdf, https://www.kidney.org/kidneydisease/howkidneyswrk, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198006/, ttps://www.asn-online.org/education/kidneyweek/2018/program-abstract.aspx?controlId=3011451, Bioinformatics and ‘omics analysis to classify patients and uncover new genetic disease drivers, The development of advanced models for target validation and understanding disease development, New modalities for previously undruggable targets. Click ‘cancel’ to return to AstraZeneca’s site or ‘continue’ to proceed. Around 40% of patients with heart failure also have CKD,2 and patients with both diabetes and early kidney disease may have a reduced life expectancy compared to a healthy person.3, The kidney has critical roles in the human physiology, removing waste products and balancing the body’s fluids. AstraZeneca will also present new insights into patientsâ experiences living with CKD as well as actionable gaps in treatment and management. Ultimately, the logical conclusion of this work would be to print all the components needed to create an entire synthetic kidney. AstraZeneca and FibroGen are committed to working with the FDA ahead of the meeting and to bringing roxadustat to patients with anemia of CKD⦠Collapse. We are working collaboratively to build – and make sense of – huge genetic datasets from real patient samples. Chronic kidney disease (CKD) is a global health problem associated with clinical complications. Many of the underlying mechanisms of CKD have been a mystery until recently. It is also involved in metabolism and vitamin D production, and produces hormones that regulate red blood cell production and blood pressure.4 This all happens as a result of complex interplay with other organs, so CKD has knock-on effects throughout the entire body.5.
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