Jardiance^® (empagliflozin) Phase III EMPA-KIDNEY trial will stop early due to clear positive efficacy in people with chronic kidney disease

Oxford, UK; Ingelheim, Germany and Indianapolis, U.S. 16 March 2022 – The EMPA-KIDNEY trial, evaluating the effect of empagliflozin in adults with chronic kidney disease (CKD), will stop early based on a recommendation from the trial’s Independent Data Monitoring Committee. This follows a formal interim assessment that met prespecified criteria for positive efficacy, announced the Medical Research Council (MRC) Population Health Research Unit at the University of Oxford, Boehringer Ingelheim, and Eli Lilly and Company (NYSE: LLY).

As the largest SGLT2 inhibitor trial in CKD to date, EMPA-KIDNEY is evaluating the efficacy and safety of empagliflozin in adults with CKD who are frequently seen in clinical practice but who have been under-represented in previous SGLT2 inhibitor trials, therefore addressing a critical unmet need. The trial includes people:^1,2 

• with mildly to severely reduced eGFR (a measure of kidney function);
• with normal and increased levels of albumin (a type of protein present in the urine);
• with and without diabetes;
• with CKD attributable to a wide range of underlying causes.

EMPA-KIDNEY is a large, double-blind, randomized, placebo-controlled, academic-led trial, including more than 6,600 adults with CKD.² The trial is being conducted, analyzed, and reported by the MRC Population Health Research Unit at the University of Oxford. The primary endpoint of the trial is a composite of kidney disease progression* or cardiovascular death. Key secondary outcomes include cardiovascular death or hospitalization for heart failure, all-cause hospitalization, and all-cause mortality.² 

“Worldwide five to ten million people die each year from chronic kidney disease and many lives are severely disrupted by dialysis treatment,” said Associate Professor William Herrington, Clinician Scientist Oxford Population Health, Honorary Consultant Nephrologist, and EMPA-KIDNEY co-Principal Investigator. “We studied a wide range of patients with declining kidney function with the aim of delaying the need for dialysis and avoiding heart disease in as many of them as possible.”

“We are thrilled that the trial has shown that empagliflozin is beneficial among the patients studied in EMPA-KIDNEY,” said Professor Richard Haynes, co-Principal Investigator. “We are very grateful to all of the participants who have made this trial possible and look forward to sharing detailed trial results later this year.”   

Kidney disease is a global public health issue, affecting nearly 850 million people, which is more than one in ten adults.^3,4  CKD is a leading cause of death globally and doubles a person’s risk for hospitalization.^5,6  Additionally, CKD is closely linked with several metabolic and cardiovascular diseases such as diabetes, high blood pressure, and obesity.^7,8,9 

“As part of the larger community dedicated to helping the millions of people living with chronic kidney disease, the early stop of EMPA-KIDNEY brings us one step closer to achieving this goal much sooner,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “EMPA-KIDNEY adds to the success of the EMPOWER trial program which has already demonstrated cardio-renal and metabolic benefits of empagliflozin for millions of people across the globe.”

Full results from the EMPA-KIDNEY trial will be presented at an upcoming medical congress.

“EMPA-KIDNEY included a range of adults with kidney disease who have been excluded from, or under-represented in, previous trials focusing on the use of SGLT2 inhibitors to slow kidney disease progression,” said Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. “The early stop of the trial is a tremendous step toward our goal of improving the lives of adults living with kidney disease.”

EMPA-KIDNEY follows the landmark EMPA-REG OUTCOME® and EMPEROR trials, all of which demonstrated cardio-renal benefits of empagliflozin.^10,11,12 EMPA-REG OUTCOME was the first SGLT2 inhibitor cardiovascular outcome trial to show benefits in both cardiovascular and kidney^† outcomes in type 2 diabetes patients with established cardiovascular disease on standard of care.¹⁰ Additionally, sub-analysis from the EMPEROR trials showed cardio-renal benefits with empagliflozin in adults with chronic heart failure, regardless of ejection fraction.^11,12 

The EMPA-KIDNEY trial is part of the EMPOWER clinical program, the broadest and most comprehensive of any SGLT2 inhibitor, exploring the impact of empagliflozin on the lives of people across the spectrum of cardio-renal-metabolic conditions.

^*Defined as end-stage kidney disease (the initiation of maintenance dialysis or receipt of a kidney transplant), a sustained decline in eGFR to below 10 mL/min/1.73 m2, renal death or a sustained decline of at least 40 percent in eGFR from randomization).

^†Secondary pre-specified exploratory endpoint: incident or worsening nephropathy, relative risk reduction of 39 percent. Defined as progression to macroalbuminuria, doubling of serum creatinine (accompanied by eGFR [MDRD] ≤45 mL/min/1.73 m2), initiation of renal replacement therapy or death from kidney disease.

eGFR, estimated glomerular filtration rate; MDRD, Modification of Diet in Renal Disease.

About chronic kidney disease 

About one third of CKD cases are attributable to metabolic conditions such as diabetes, obesity, and hypertension.^13,14 

Notably, CKD is associated with increased morbidity and mortality. The majority of deaths among people with CKD occur as a result of cardiovascular complications, often before reaching end-stage kidney disease.^15,16  Once end-stage kidney disease is reached, affected individuals have to undergo kidney replacement treatments, such as regular dialysis or kidney transplantation.¹⁷  CKD is highly prevalent in various parts of the world, affecting more than ten percent of the population.^14,15

About EMPA-KIDNEY: The study of heart and kidney protection with empagliflozin^2,16

EMPA-KIDNEY (NCT03594110) is a multinational randomized, double-blind, placebo-controlled clinical trial, designed to evaluate the effect of empagliflozin on kidney disease progression and cardiovascular mortality risk. The primary outcome is defined as time to a first event of either 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 <10 mL/min/1.73 m², renal death, or a sustained decline of ≥40 percent in eGFR from randomization. EMPA-KIDNEY includes more than 6,600 adults with established CKD both with and without diabetes, as well as with and without albuminuria, receiving either empagliflozin 10 mg or placebo, on top of current standard of care. 

About the Medical Research Council (MRC) Population Health Research Unit (PHRU) at the University of Oxford

The MRC PHRU at the University of Oxford, part of Oxford Population Health, improves the treatment and prevention of chronic diseases, particularly cardiovascular disease and metabolic disease (such as diabetes mellitus and CKD), which collectively account for a large proportion of premature adult deaths and the burden of disability worldwide. MRC PHRU is led by EMPA-KIDNEY Steering Committee co-chair Professor Colin Baigent. MRC PHRU coordinates innovative clinical trials and meta-analyses that have a major impact on health. Other major studies include the ground-breaking Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial which is co-led by EMPA-KIDNEY Steering Committee co-chair, Professor Sir Martin Landray. MRC PHRU’s worldwide approach, involving the study of large numbers of people, provides reliable information about the causes of disease and the effects of treatments, and has had a major impact on global health.

About the EMPOWER program

The Alliance has developed the EMPOWER program to explore the impact of empagliflozin on major clinical cardiovascular and renal outcomes in a spectrum of cardio-renal-metabolic conditions. Cardio-renal-metabolic conditions are the leading cause of mortality worldwide and account for up to 20 million deaths annually.¹⁸  Through the EMPOWER program, Boehringer Ingelheim and Lilly are working to advance knowledge of these interconnected systems and create care which offers integrated, multi-organ benefits. Comprised of nine clinical trials and two real-world evidence studies, EMPOWER reinforces the long-term commitment of the Alliance to improve outcomes for people living with cardio-renal-metabolic conditions. With more than 400,000 adults enrolled worldwide in clinical trials, it is the broadest and most comprehensive clinical program for an SGLT2 inhibitor to date. 

About cardio-renal-metabolic conditions

Boehringer Ingelheim and Lilly are driven to transform care for people with cardio-renal-metabolic conditions, a group of interconnected disorders that affect more than one billion people worldwide and are a leading cause of death.²⁰

The cardiovascular, renal and metabolic systems are interconnected, and share many of the same risk factors and pathological pathways along the disease continuum. Dysfunction in one system may accelerate the onset of others, resulting in progression of interconnected diseases such as type 2 diabetes, cardiovascular disease, heart failure, and kidney disease, which in turn leads to an increased risk of cardiovascular death. Conversely, improvements in one system can lead to positive effects throughout the others.^7,19,20 

Through our research and treatments, our goal is to support people’s health, restoring the balance between the interconnected cardio-renal-metabolic systems and reducing their risk of serious complications. As part of our commitment to those whose health is jeopardized by cardio-renal-metabolic conditions, we will continue embracing a multidisciplinary approach towards care and focusing our resources on filling treatment gaps.

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 its label in several countries.^21,22 

Boehringer Ingelheim and Eli Lilly and Company

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an Alliance that centers on compounds representing several of the largest diabetes treatment classes. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributing to the Alliance. The Alliance leverages the strengths of two of the world’s leading pharmaceutical companies to focus on patient needs. By joining forces, the companies demonstrate their commitment, not only to the care of people with diabetes, but also to investigating the potential to address areas of unmet medical need. Clinical trials have been initiated to evaluate the impact of empagliflozin on people living with heart failure or CKD.

About Boehringer Ingelheim 

Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Around 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.com.

About Eli Lilly and Company

Lilly is a global health care leader that unites caring with discovery to create medicines that 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 lilly.com and lilly.com/newsroom.

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 Jardiance as a treatment for adults with type 2 diabetes, to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease, and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, and as a potential treatment for adults with cardio-renal-metabolic conditions and reflects Lilly’s current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date or that Jardiance will receive additional regulatory approvals. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly’s expectations, please see Lilly’s most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

CONTACTS:

Sarah Reimer
Boehringer Ingelheim 
Email: press@boehringer-ingelheim.com    
Phone: +49 (6132) 77-2093
 

Stephan Thalen 
Eli Lilly and Company
Email: stephan.thalen@lilly.com  
Phone: +1 (317) 903-5640

Anne Whitehouse 
Director of Communications and Public Engagement, Oxford Population Health
Phone: +44 (0) 1865 289474
Mobile: +44 (0) 7812 165934 
 

References:

___________________

¹ Herrington WG, Preiss D, Haynes R, et al. The potential for improving cardio-renal outcomes by sodium-glucose co-transporter-2 inhibition in people with chronic kidney disease: a rationale for the EMPA-KIDNEY study. Clin Kidney J. 2018;11(6):749–61.

²  The EMPA-KIDNEY Collaborative Group. [Published online ahead of print March 3 2022]. Nephrol Dial Transplant. 2022. DOI:10.1093/ndt/gfac040. 

³  Li PKT, Garcia-Garcia G, Lu SF, et al. Kidney health for everyone everywhere – from prevention to detection and equitable access to care. Braz J Med Biol Res. 2020;53(3):e9614.

⁴  Luyckx VA, Al-Aly Z, Bello AK, et al. Sustainable Development Goals relevant to kidney health: an update on progress. Nature Reviews Nephrology. 2021;17:15–32.

⁵  Neuen BL, Chadban SJ, Demaio AR, et al. Chronic kidney disease and the global NCDs agenda. BMJ Glob Health. 2017;2(2):e000380.

⁶  USRDS. 2021 Annual Report. Chronic Kidney Disease: Morbidity and Mortality in Patients with CKD. Available at: https://adr.usrds.org/2021/chronic-kidney-disease/3-morbidity-and-mortality-in-patients-with-ckd. Last accessed: March 2022. 

⁷  Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2016;12(2):73-81.

⁸  Pugh D, Gallacher PJ, Dhaun N. Management of hypertension in chronic kidney disease. Drugs. 2019;79(4):365-379.

⁹  Kovesdy CP, Furth SL, Zoccali C. Obesity and kidney disease: hidden consequences of the epidemic. Am J Nephrol. 2017;45:283-291.

¹⁰  Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375:323-34.

¹¹  Anker S, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385:1451-1461.

¹²  Packer MD, Anker S, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020; 383:1413-1424.

¹³  Yim HE, Yoo KH. Obesity and chronic kidney disease: prevalence, mechanism, and management. Clin Exp Pediatr. 2021;64(10):511-518.

¹⁴ 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.

¹⁵  Coresh J. Update on the Burden of CKD. J Am Soc Nephrol. 2017;28(4):1020–1022.

¹⁶  Clinical Trials. EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin). Available at: https://clinicaltrials.gov/ct2/show/NCT03594110 Last accessed: March 2022.

¹⁷  Bello K, Levin A, Lunney M, et al. Status of care for end stage kidney disease in countries and regions worldwide: international cross-sectional survey. BMJ. 2019;367:l5873.

¹⁸  GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1459–544.

¹⁹  García-Donaire JA, Ruilope LM. Cardiovascular and Renal Links along the Cardiorenal Continuum. Int J Nephrol. 2011;2011:975782.

²⁰  Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246–58.

²¹  Jardiance® (empagliflozin) tablets. European Product Information, approved April 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_en.pdf. Last accessed: March 2022.

²² Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Last accessed: March 2022.