Ingelheim, Germany, and Indianapolis, US, 10 June 2019 – Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) today announced results of a new post-hoc analysis of data from the EMPA-REG OUTCOME® trial. These results indicated that the effect of empagliflozin on reducing cardiovascular and renal risk was consistent between a sub-group of adults with type 2 diabetes and established cardiovascular disease, who also have a form of chronic kidney disease without overt proteinuria (high levels of protein in the urine), and all others in the trial.1 The results were shared as an oral presentation at the 79th American Diabetes Association (ADA) Scientific Sessions® on 10 June in San Francisco, California, US.
“We are pleased to share new research data from the landmark EMPA-REG OUTCOME® trial, examining the effects of empagliflozin in adults with type 2 diabetes who have an increasingly common, yet infrequently studied, form of chronic kidney disease,” said Waheed Jamal, MD, Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “The results support the need for additional studies aimed at addressing important unmet medical needs for people with various forms of kidney disease. To that end, we have initiated a large outcomes trial, EMPA-KIDNEY, to investigate the effects of empagliflozin on cardiovascular death and the progression of kidney disease in a broad population of adults with chronic kidney disease.”
Globally, more than 500 million people are affected by chronic kidney disease, up to 40 percent of whom have diabetes.2,3,4 Chronic kidney disease is typically accompanied by the presence of varying amounts of protein in the urine, known as proteinuria.5 The majority of people with chronic kidney disease, however, have normal to moderately-increased urinary protein levels, rather than overt proteinuria.5 Kidney disease without overt proteinuria is becoming more common yet is rarely studied in clinical trials, despite the known increased risk for adverse outcomes.5
In this new post-hoc analysis, the effect of empagliflozin on reducing the risk of cardiovascular and kidney outcomes was consistent between people in the EMPA-REG OUTCOME® trial who had chronic kidney disease without overt proteinuria and all others in the trial.1 Outcomes examined included cardiovascular death, hospitalisation for heart failure, new or worsening kidney disease, and the combination of cardiovascular death or hospitalisation for heart failure, as well as safety outcomes of interest.1
Furthermore, results from a separate post-hoc analysis recently presented at the ISN World Congress of Nephrology 2019, indicated that the effect of empagliflozin on the cardiorenal outcome*, was consistent between people in the EMPA-REG OUTCOME® trial who had proteinuric kidney disease and all others in the trial. Together, these post-hoc analyses suggest that the effect of empagliflozin on cardiorenal outcomes is consistent regardless of whether patients have proteinuric kidney disease or not.
“These new findings are just one part of a broad and comprehensive clinical development programme that explores how empagliflozin can improve patient health outcomes and fill therapeutic gaps to serve as a broad cardiometabolic treatment option,” said Sherry Martin, MD, Vice President, Medical Affairs, Lilly. “We look forward to gathering additional information through results from EMPA-KIDNEY, which will examine the potential for empagliflozin to improve outcomes for people with chronic kidney disease, including those with and without proteinuria.”
EMPA-KIDNEY will enrol approximately 5,000 adults with chronic kidney disease both with and without diabetes as well as with and without proteinuria worldwide.6
About EMPA-KIDNEY: The study of heart and kidney protection with empagliflozin6
EMPA-KIDNEY (NCT03594110) is a multinational randomised, double-blind, placebo-controlled clinical trial, designed to evaluate the effect of empagliflozin on clinically relevant outcomes: kidney disease progression and cardiovascular mortality risk. The primary outcome is defined as time to a first event of either a cardiovascular death or kidney disease progression, defined as end-stage kidney disease (the need for kidney replacement therapy such as, dialysis or kidney transplantation), a sustained decline in eGFR to <10mL/min/1.73m2, renal death or a sustained decline of ≥40 percent in eGFR from randomisation. EMPA-KIDNEY includes people with established chronic kidney disease both with and without diabetes, receiving either empagliflozin 10 mg or placebo, on top of current standard of care.
EMPA-KIDNEY is an academic collaboration, independently conducted, analysed and reported by the Medical Research Council Population Health Research Unit at the University of Oxford (MRC PHRU), which is based in the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU). Boehringer Ingelheim and Lilly are providing the funding for the study as part of their commitment to advancing treatments and pioneering research to address the public health challenges of cardiovascular, metabolic and kidney diseases beyond type 2 diabetes.
About Chronic Kidney Disease
Chronic kidney disease is defined as a progressive decline of kidney function over time. About two thirds of chronic kidney disease cases are attributable to metabolic conditions such as diabetes (known as diabetic kidney disease), obesity and hypertension.7,8,9
Notably, chronic kidney disease is associated with increased morbidity and mortality. The majority of deaths among people with chronic kidney disease occur as a result of cardiovascular complications, often before reaching end-stage kidney disease.10,11,12 Once end-stage kidney disease is reached, affected individuals have to undergo kidney replacement treatments, such as chronic dialysis or kidney transplantation.13 Chronic kidney disease is highly prevalent in various parts of the world, affecting more than 10 percent of the population.14 Since there is currently no approved treatment available to specifically reduce kidney disease progression and cardiovascular death, the overarching unmet medical need for new treatment options in people with chronic kidney disease is evident.
About Empagliflozin
Empagliflozin (marketed as Jardiance®) is an oral, once daily, highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medicine to include cardiovascular death risk reduction data in the label in several countries.15,16,17
Inhibition of SGLT2 with empagliflozin in people with type 2 diabetes and high blood sugar levels leads to excretion of excess sugar in the urine. In addition, initiation of empagliflozin increases excretion of salt from the body and reduces the fluid load of the body’s blood vessel system (i.e. intravascular volume). Empagliflozin induces changes to the sugar, salt and water metabolism in the body that may contribute to the reductions in cardiovascular death observed in the EMPA-REG OUTCOME® trial.
About Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centers on compounds representing several of the largest diabetes treatment classes. The alliance leverages the strengths of two of the world’s leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of people with diabetes and stand together to focus on patient needs. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributed to the alliance.
Boehringer Ingelheim
Improving the health of humans and animals is the goal of the research-driven pharmaceutical company Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention.
Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas human pharmaceuticals, animal health and biopharmaceuticals. In 2018, Boehringer Ingelheim achieved net sales of nearly 17.5 billion euros. R&D expenditure of almost 3.2 billion euros, corresponded to 18.1 percent of net sales.
As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment.
More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: http://annualreport.boehringer-ingelheim.com.
About Lilly Diabetes
Lilly has been a global leader in diabetes care since 1923, when we introduced the world's first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research and collaboration, a wide range of therapies and a continued determination to provide real solutions – from medicines to support programmes and more – we strive to make life better for all those affected by diabetes around the world. For more information, visit www.lillydiabetes.com.
About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at http://www.lilly.com/ and https://newsroom.lilly.com/social-channels.
Intended audiences
This press release is issued from Boehringer Ingelheim Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where Boehringer Ingelheim and Eli Lilly and Company do business.
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about clinical trials to evaluate empagliflozin as a treatment for adults with chronic kidney disease and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that empagliflozin will receive additional regulatory approvals. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
CONTACT:
Dr Petra Kienle
Product Communication Manager
Boehringer Ingelheim
Email: press@boehringer-ingelheim.com
Phone: +49 (6132) 77 143877
Stephan Thalen
Global Business Communications
Lilly Diabetes
Email: stephan.thalen@lilly.com
Phone: +1 (317) 276 8304
Footnotes
*Defined as end-stage kidney disease (initiation of maintenance renal replacement therapy or sustained eGFR <15 ml/min/1.73m2), sustained doubling or creatinine, or renal/cardiovascular death.
References
1 Inzucchi SE, Zinman B, George JT, et al. Empagliflozin and cardiorenal outcomes in patients with non-proteinuric kidney disease in the EMPA-REG OUTCOME trial. Presented the American Diabetes Association (ADA) 79th Scientific Sessions®. 10 June 2019, San Francisco, California, US.
2 George C, Mogueo A, Okpechi I, et al. Chronic kidney disease in low-income to middle-income countries: the case for increased screening. BMJ Glob Health 2017;2:e000256. doi:10.1136/bmjgh-2016-000256.
3 International Diabetes Foundation. Diabetes Atlas 8th Edition. Available at: http://www.diabetesatlas.org. Accessed May 2019.
4 Yee J. Diabetic Kidney Disease: Chronic Kidney Disease and Diabetes. Diabetes Spectrum 2008; 21(1):8-10.
5 Bolignaro B and Zoccali C. Non-proteinuric rather than proteinuric renal diseases are the leading cause of end-stage kidney disease. Nephrology Dialysis Transplantation. 2017;32(2):194-99.
6 EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin. Available at: https://clinicaltrials.gov/ct2/show/NCT03594110. Accessed May 2019.
7 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.
8 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).
9 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.
10 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.
11 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.
12 Schiffrin EL, Lipman ML and Mann JFE. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85-97.
13 American Kidney Fund. Kidney Failure (ESRD) Causes, Symptos, & Treatments. Available at: http://www.kidneyfund.org/kidney-disease/kidney-failure/. Accessed May 2019.
14 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.
15 Jardiance® (empagliflozin) tablets U.S. Prescribing Information. Available at: https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed May 2019.
16 European Summary of Product Characteristics Jardiance®, approved May 2018. Data on file.
17 Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.