• EMPA-KIDNEY is the largest and broadest dedicated SGLT2 inhibitor trial in chronic kidney disease to date
  • Detailed results are expected to be presented later this year

Dubai, United Arab Emirates – 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]

"At Boehringer Ingelheim, our goal is to create innovation to make breakthrough therapies that improve the lives of patients. There are millions of patients across the globe living with chronic kidney disease who are at risk of worsening kidney function and heart problems. The clear evidence of the positive efficacy of empagliflozin in adults with chronic kidney disease is a significant milestone. The early stop of EMPA-KIDNEY trial has accelerated our timelines, helping us deliver a potential treatment option for people with chronic kidney disease earlier than expected," said Mohammed Al-Tawil, Regional Managing Director and Head of Human Pharma at Boehringer Ingelheim India, Middle East, Turkey and Africa (‘IMETA’).

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

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.

-Ends-

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 empagliflozin2,16

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 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]

About Boehringer Ingelheim

Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. 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. More than 52,000 employees serve over 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.com

Intended audiences

This press release is issued from the Boehringer Ingelheim Regional Headquarters in Dubai, UAE, and is intended to provide information about Boehringer Ingelheim’s global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and other press releases 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.

CONTACTS:
Feda Kassem
Manager, Human Pharma and Animal Health Communications IMETA, Corporate Affairs
India, Middle East, Turkey and Africa
Boehringer Ingelheim 
Email: feda.kassem@boehringer-ingelheim.com

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.