Boehringer Ingelheim and Eli Lilly Announce Collaboration with University of Oxford to Study Empagliflozin in Chronic Kidney Disease Patients
Boehringer Ingelheim
Developer of Innovative Drugs and Therapies
University of Oxford
The University of Oxford (commonly referred to as "Oxford") is a public research university located in Oxford, England. Operating under a collegiate federal system, it is collectively known with the University of Cambridge as "Oxbridge." Together with the University of Cambridge, University College London, Imperial College London, and the London School of Economics and Political Science, it forms the "G5 Super Elite Universities."While the exact founding date of the University of Oxford is lost to history, archival records clearly indicate that teaching commenced as early as 1096. The university experienced rapid development after receiving substantial support from the English royal family in 1167. It is the oldest university in the English-speaking world and the second-oldest surviving higher education institution globally. The University of Oxford holds prestigious academic standing and extensive influence in fields such as mathematics, physics, medicine, law, and business, and is widely recognized as one of the world’s leading higher education institutions. In the 2017–18 Times Higher Education World University Rankings, Oxford ranked first worldwide; in the Academic Ranking of World Universities (ARWU), it ranked seventh globally.On December 18, 2018, the "2018 World Brand 500" list, compiled by the World Brand Lab, was released, with the University of Oxford ranked 99th.
Eli Lilly
Global Pharmaceutical R&D and Production Company
- University of OxfordJiangStudy of EmpagliflozinNetFor chronic useKidneyPatientEffects on Cardiovascular and Renal Diseases
- MakeForEmpagliflozinNet Clinical Research ItemsPart of the objective,EMPA-KIDNEY The study will explore empagliflozinEfficacy and Safety in a Broad Patient Population and Across Diverse Clinical Settings
INGELHEIM, Germany and INDIANAPOLIS, April 19, 2018 /PRNewswire/ -- Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) today announced an academic collaboration with the University of Oxford. The EMPA-KIDNEY study will investigate the effect of empagliflozin on the progression of kidney disease and cardiovascular death in patients with chronic kidney disease, regardless of whether they have diabetes. The Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, established based on the Clinical Trial Service Unit and Epidemiological Studies Unit, will be independently responsible for conducting, analyzing, and reporting the study. Boehringer Ingelheim and Eli Lilly and Company will provide funding for the research.
This dedicated patient outcomes study conducted in patients with chronic kidney disease is based on the prior EMPA-REG OUTCOME® Based on the landmark EMPA-REG OUTCOME® trial, which was conducted in patients with type 2 diabetes and cardiovascular disease to evaluate the effect of adding empagliflozin versus placebo on cardiovascular outcomes in addition to standard care.1Participating in the EMPA-REG OUTCOME®Approximately one-third of the patients in the trial had chronic kidney disease at enrollment. The secondary, exploratory endpoints of this study provided promising data regarding the reduction in the relative risk of new-onset or worsening kidney disease. The EMPA-KIDNEY study will help to further elucidate these findings.1,2
“EMPA-REG OUTCOME®“Trial data suggest that empagliflozin may have the potential to reduce the risk of kidney disease progression and cardiovascular events in patients with chronic kidney disease,” said the head of the Medical Research Council Population Health Research Unit at the University of Oxford, UK.Colin Baigent“The number of patients with chronic kidney disease worldwide exceeds 200 million, many of whom face a significant risk of progression to end-stage renal disease. Furthermore, the risk of premature death due to cardiovascular disease among patients with chronic kidney disease is increasingly elevated. Given the substantial unmet medical need in this field, we are pleased to explore through the EMPA-KIDNEY study whether empagliflozin can emerge as a novel therapeutic option to improve the lives of patients with chronic kidney disease,” said the professor.
The EMPA-KIDNEY study will enroll 5,000 patients with chronic kidney disease (with or without diabetes). The primary outcome is to evaluate the effect of empagliflozin on time to progression to clinically relevant kidney disease or cardiovascular death. This study is also part of the empagliflozin clinical research program, which is the largest clinical research program for SGLT2 (sodium-glucose cotransporter-2) inhibitors.
“We are delighted to collaborate with a top-tier institution like the University of Oxford. Scientists at the University of Oxford have long been renowned for conducting innovative clinical trials that transform the treatment landscape in patients with chronic kidney disease,” said the Senior Vice President of Cardiovascular Metabolic Therapies at Boehringer Ingelheim.Georg van Husen“The better understanding and improvement of the treatment for chronic kidney disease is our shared interest and commitment. We are very excited to further explore the potential of empagliflozin in new disease areas,” said the doctor.
“Based on EMPA-REG OUTCOME®“The EMPA-KIDNEY study, building on the trial results, will further expand our understanding of how empagliflozin affects the lives of a broad patient population, regardless of whether they have diabetes.” — Vice President of Diabetes Product Development, Eli LillyJeff EmmickThe PhD added, “We are highly enthusiastic about this new collaboration and the progress of the subsequent EMPA-KIDNEY study.”
About the University of OxfordMRC Population Health Research Unit (MRC PHRU)
MRC Population Health Research Unit (MRC PHRU), University of Oxford (https://www.mrc-phru.ox.ac.uk/) Dedicated to the treatment and prevention of chronic diseases, particularly cardiovascular and metabolic disorders (such as diabetes and chronic kidney disease), which together account for a substantial proportion of premature deaths and disabilities worldwide. The MRC PHRU pioneers innovative clinical research and meta-analyses aimed at identifying significant advances with major implications for health. Its research spans the globe, encompassing large populations, and provides robust evidence on disease etiology and therapeutic effects, thereby exerting a profound impact on global human health.
AboutEMPA-KIDNEY: EmpagliflozinNet Research on Cardiac and Renal Protection
The EMPA-KIDNEY trial is a multinational, randomized, double-blind, placebo-controlled clinical study. This study aims to evaluate the impact of empagliflozin on two clinically relevant outcomes: progression of kidney disease and risk of cardiovascular death. The primary outcome is defined as the time to the first occurrence of either cardiovascular death or progression of kidney disease. Progression of kidney disease is defined as end-stage kidney disease (requiring renal replacement therapy, such as dialysis or kidney transplantation).3, with a sustained decline in eGFR to <10 mL/min/1.73m2 , death due to kidney disease or a sustained decline in eGFR of ≥40% from the start of random sampling. EMPA-KIDNEY will enroll patients with chronic kidney disease receiving current standard of care, regardless of whether they have comorbid diabetes.
The study will be conducted across multiple countries to reflect the global situation, with a plan to randomly assign approximately 5,000 patients to receive either 10 mg of empagliflozin daily or a placebo in addition to their standard treatment.
Regarding ChronicKidneyDisease
Chronic kidney disease is a condition characterized by the gradual decline of renal function over time. Approximately two-thirds of chronic kidney disease cases are caused by metabolic disorders such as diabetes, obesity, and hypertension.4,5,6
Notably, the incidence and mortality rates of chronic kidney disease are increasing year by year. Most patients with chronic kidney disease often die from cardiovascular complications before reaching end-stage renal disease.7,8,9Once end-stage renal disease (ESRD) is reached, patients require renal replacement therapy, such as chronic dialysis or kidney transplantation.3Chronic kidney disease is highly prevalent worldwide, affecting approximately one-tenth of the global population.10Given the current lack of approved therapies to reduce the progression of kidney disease and cardiovascular mortality, there is clearly a substantial unmet medical need for new treatment options in patients with chronic kidney disease.
AboutEMPA-REG OUTCOME®1,2
EMPA-REG OUTCOME® is a long-term, multicenter, randomized, double-blind, placebo-controlled trial conducted in more than 7,000 patients with type 2 diabetes and cardiovascular disease from 42 countries.
The study aimed to evaluate the differential effects of adding empagliflozin (10 mg or 25 mg once daily) versus placebo to standard therapy. Standard therapy included glucose-lowering agents and cardiovascular medications (including antihypertensive and cholesterol-lowering drugs). The primary endpoint was defined as the time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
Despite EMPA-REG OUTCOME® The trial was not originally designed to evaluate the potential mechanisms underlying the effect of empagliflozin on renal outcomes; however, renal assessment was indeed one of the prespecified analyses in the statistical analysis plan for the secondary endpoints.
The overall safety profile of empagliflozin demonstrated in the EMPA-REG OUTCOME® trial was consistent with that observed in previous trials.
About EmpagliflozinNet
Empagliflozin (brand name Jardiance®) is an oral, once-daily, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medication with labeling in several countries indicating a reduction in cardiovascular death.。11,12,13The indication for empagliflozin in China is the treatment of type 2 diabetes mellitus. In conjunction with diet and exercise, it may be used as monotherapy or in combination with metformin, or with both metformin and sulfonylureas, to improve glycemic control in patients with type 2 diabetes mellitus.
Empagliflozin helps patients with type 2 diabetes and hyperglycemia excrete excess glucose in the urine by inhibiting SGLT2. In addition, empagliflozin increases the excretion of salt (i.e., sodium) from the body and reduces fluid load on the vascular system (i.e., intravascular volume). EMPA-REG OUTCOME® Trial data demonstrate that empagliflozin can induce changes in glucose, salt, and water metabolism in vivo, thereby reducing the risk of cardiovascular death.
Empagliflozin is contraindicated in patients with type 1 diabetes mellitus or diabetic ketoacidosis.
Boehringer Ingelheim and Eli Lilly
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced a collaborative agreement in the field of diabetes treatment, covering three compounds representing some of the largest drug classes. This partnership combines the strengths of two global leading pharmaceutical companies, integrating Boehringer Ingelheim’s solid foundation in innovative research and development with Eli Lilly and Company’s innovative research, extensive experience, and pioneering history in diabetes care. Through this collaboration, both companies are committed to helping patients with diabetes and focusing on their clinical needs.
For more information on collaboration, please visitwww.boehringer-ingelheim.cnorwww.lillychina.com
References
[1] Zinman B., et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 10.156 (2015).
[2] Wanner C, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323-334.
[3] American Kidney Fund. Kidney Failure (ESRD) Causes, Symptos, & Treatments. Available at: http://www.kidneyfund.org/kidney-disease/kidney-failure/. Accessed March 2018.
[4] Levin A, Tonelli M, Bonventre J, et al. Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy. Lancet 2017;390:1888-917.
[5] United States Renal Data System, USRDS 2012 Annual data report: Atlas of chronic kidney disease and end-stage renal disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2012. Available from: http://www.usrds.org/reference.htm. See Appendix I, United States Renal Data System (USRDS).
[6] Liyanage T, Ninomiya T, Jha V, et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. Lancet 2015; 385(9981):1975-82.
[7] Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension 2003;42:1050-65.
[8] Tonelli M, Wiebe N, Culleton B, et al. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol. 2006;17:2034-47.
[9] Schiffrin EL, Lipman ML and Mann JFE. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85-97.
[10] Eckardt K-U, Coresh J, Devuyst O, et al. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 2013;382:158-69.
[11] Jardiance® (empagliflozin) tablets U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed March 2018.
[12] European Summary of Product Characteristics Jardiance®, approved January 19, 2017. Data on file.
[13] Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.