EMPA-KIDNEY Phase III Trial of Empagliflozin in Chronic Kidney Disease Terminated Early Due to Clear Efficacy
Boehringer Ingelheim
Developer of Innovative Drugs and Therapies
Eli Lilly
Global Pharmaceutical R&D and Production Company
University of Oxford
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Oxford, UK, Ingelheim, Germany and Indianapolis, US, March 18, 2022 /PRNewswire/ -- The Medical Research Council (MRC) Population Health Research Unit at the University of Oxford, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced that the EMPA-KIDNEY clinical trial will be stopped early based on the recommendation of the independent data monitoring committee for the clinical trial. This clinical trial evaluates the efficacy of empagliflozin in treating adult patients with chronic kidney disease (CKD). The decision was made after a formal interim analysis, which met the pre-specified positive efficacy criteria. As the largest clinical trial to date investigating SGLT-2 inhibitors in CKD, EMPA-KIDNEY is evaluating the efficacy and safety of empagliflozin in adult patients with CKD, including populations commonly seen in clinical practice but underrepresented in previous SGLT2 inhibitor trials, aiming to address key unmet clinical needs. The population included in the trial consists of:[1],[2]
EMPA-KIDNEY is a large, double-blind, randomized, placebo-controlled clinical trial led by academic institutions, enrolling more than 6,600 adult patients with CKD.[2]The trial was independently conducted, analyzed, and reported by the MRC Population Health Research Unit at the University of Oxford. The primary endpoint of the trial was a composite of renal disease progression* or cardiovascular death. Key secondary endpoints included cardiovascular death or hospitalization for heart failure, all-cause hospitalization, and all-cause mortality.[2]
“5 to 10 million people die of chronic kidney disease worldwide each year, and the lives of many patients are severely affected by frequent dialysis treatments.”Associate Professor William Herrington, a clinical scientist in population health at the University of Oxford, honorary consultant in nephrology, and co-principal investigator of EMPA-KIDNEY, said.“The purpose of conducting this study in a wide range of patients with declining kidney function is to delay the need for dialysis as much as possible and prevent the occurrence of heart disease.”
“We are pleased that clinical trials have shown empagliflozin to be beneficial for patients included in the EMPA-KIDNEY study.”Co-Chief InvestigatorRichard HaynesThe professor said.“We are extremely grateful to all the participants who made this trial possible, and we look forward to sharing detailed results later this year.”
Kidney disease is a global public health problem, affecting nearly 850 million people, which is more than one-tenth of the adult population.[3],[4]CKD is a leading cause of death among patients worldwide and doubles the risk of hospitalization.[5],[6]In addition, CKD is closely related to various metabolic and cardiovascular diseases, such as diabetes, hypertension, and obesity.[7],[8]
“As part of our commitment to helping millions of people with chronic kidney disease, the early termination of the EMPA-KIDNEY clinical trial brings us closer to achieving this goal more quickly.”Waheed Jamal, MD, Vice President of Boehringer Ingelheim and Head of Cardiovascular Metabolic Medicine, said.“EMPA-KIDNEY further highlights the success of the EMPOWER trial program, which has already demonstrated the cardio-renal-metabolic benefits of empagliflozin for millions of patients worldwide.”
The full results of the EMPA-KIDNEY clinical trial will be announced at an upcoming medical conference.
“EMPA-KIDNEY included a broad range of adult patients with kidney disease who were excluded from or did not meet the inclusion criteria for previous trials, which focused on studying SGLT2 inhibitors to slow the progression of kidney disease.”Jeff Emmick, M.D., Vice President of Product Development at Eli Lilly and Company, said.“The early termination of the clinical trial is a significant step towards our goal of improving the lives of adult patients with kidney disease.”
EMPA-KIDNEY was conducted following the landmark EMPA-REG OUTCOME® and EMPEROR clinical trials, all of which demonstrated the cardio-renal benefits of empagliflozin.[9],[11],[12]EMPA-REG OUTCOME is the first cardiovascular outcome trial of an SGLT2 inhibitor, showing that empagliflozin, when added to standard care, reduces cardiovascular and renal risk in patients with type 2 diabetes and established cardiovascular disease.**All outcomes were beneficial.[10]In addition, a subgroup analysis of the EMPEROR trial showed that empagliflozin demonstrated cardio-renal benefits in adult patients with chronic heart failure, regardless of ejection fraction.[10],[11]
The EMPA-KIDNEY trial is part of the EMPOWER clinical program, which is currently the broadest and most comprehensive clinical research initiative among all SGLT2 inhibitors, aiming to explore the impact of empagliflozin on the lives of patients with various cardio-renal-metabolic conditions.
*Defined as end-stage renal disease (initiation of maintenance dialysis or receipt of kidney transplantation),eGFRContinuously decreased to below10 mL/min/1.73 m2, Renal death or after randomization eGFRContinuously decreasing for at least 40%。
**Pre-specified secondary exploratory endpoint: Renal events or worsening, relative risk reduction 39%. Defined as progression to heavy albuminuria, doubling of serum creatinine (witheGFR [MDRD] Less than or equal to45 mL/min/1.73 m2), initiation of renal replacement therapy, or death from renal disease.
eGFREvaluate Glomerular Filtration Rate;MDRD：Changes in the diet for kidney disease.
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] 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.
[10] 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.
[11] 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.
[12] Yim HE, Yoo KH. Obesity and chronic kidney disease: prevalence, mechanism, and management. Clin Exp Pediatr. 2021;64(10):511-518.
[13] 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.
[14] Coresh J. Update on the Burden of CKD. J Am Soc Nephrol. 2017;28(4):1020–1022.
[15] 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.
[16] 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.
[17] García-Donaire JA, Ruilope LM. Cardiovascular and Renal Links along the Cardiorenal Continuum. Int J Nephrol. 2011;2011:975782.
[18] Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246–58.
[19] 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.
[20] Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Last accessed: March 2022.