Landmark EMPA-KIDNEY trial showed significant benefit of empagliflozin in reducing kidney disease progression or cardiovascular death by 28% vs. placebo in people with chronic kidney disease

EMPA-KIDNEY Phase III clinical trial met its primary endpoint by demonstrating a significant kidney and cardiovascular benefit for adults living with chronic kidney disease (CKD).^1,2  When treated with empagliflozin, the risk of kidney disease progression or cardiovascular death was significantly reduced by 28% vs. placebo (HR; 0.72; 95% CI 0.64 to 0.82; P<0.000001).^1,2 The results were announced earlier this month during the American Society of Nephrology (ASN)’s Kidney Week 2022 by the Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford which designed, conducted and analyzed EMPA-KIDNEY, in a scientific collaboration with Boehringer Ingelheim. The results were also published simultaneously in The New England Journal of Medicine.

EMPA-KIDNEY is the first SGLT2 inhibitor CKD trial to demonstrate a significant reduction in all-cause hospitalizations (14%) (HR; 0.86; 95% CI 0.78 to 0.95; p=0.0025) vs. placebo, one of the pre-specified key secondary confirmatory endpoints,^1,2  CKD doubles a person’s risk for hospitalization and is a leading cause of death globally.^1,2 Hospitalizations account for 35%-55% of total healthcare costs for people with CKD in the U.S.³

The overall safety data was generally consistent with previous findings, confirming the well-established safety profile of empagliflozin.

“We know that there is an urgent need for new therapies proven to delay CKD progression which can lead to the need for dialysis or transplantation. Today’s results demonstrate that empagliflozin may benefit adults at risk of progression, including those with or without diabetes, and across a wide range of kidney function,” said William Herrington, Associate Professor at MRC PHRU (part of Oxford Population Health), and Honorary Consultant Nephrologist, and EMPA-KIDNEY co-Principal Investigator. “By reducing the risk of kidney disease progression or cardiovascular death, empagliflozin has the potential to positively impact healthcare systems worldwide.”

“The design of the EMPA-KIDNEY trial included a wider range of patients than ever before,” said Professor Richard Haynes, co-Principal Investigator. “Previous SGLT2 inhibitor trials focused on certain groups of people living with CKD, such as those with diabetes or high levels of protein in their urine. Today’s positive trial results across a broad CKD population reflect an opportunity to improve the treatment of this disease and prevent people from needing dialysis.”

EMPA-KIDNEY is the largest and broadest dedicated SGLT2 inhibitor trial to date.⁴ It included 6,609 participants across a wide range of underlying causes, many with comorbidities across the spectrum of cardiovascular, kidney, or metabolic conditions. The trial assessed both kidney and cardiovascular outcomes in people across the spectrum of CKD severity.⁵

Mohammed Al-Tawil, Regional Managing Director and Head of Human Pharma at Boehringer Ingelheim India, the Middle East, Turkey, and Africa (IMETA) said, “At Boehringer Ingelheim, our goal is to develop breakthrough therapies that bridge existing medical gaps. With around 10% of the global population being affected by CKD, there is a pressing need for new therapies that can effectively delay the progression of the disease. We are very proud of our positive EMPA-KIDNEY trial results which reinforce the potential role of empagliflozin in transforming the management of interconnected conditions to benefit patients and overburdened systems alike.”

Reductions in other key secondary endpoints of hospitalization for heart failure or cardiovascular death or all-cause death were not statistically significant, however the power to detect this was limited by the number of events observed. Reduction in the risk of these endpoints is consistent with the totality of the evidence from other trials which have shown statistical significance of these outcomes.

-ENDS-

Notes to editors

Kidney disease progression: Defined as end-stage kidney disease (the initiation of maintenance dialysis or receipt of a kidney transplant), a sustained decline in estimated glomerular filtration rate (eGFR) to below 10 mL/min/1.73 m², kidney death or a sustained decline of at least 40 percent in eGFR from randomization).

End stage kidney disease: Includes initiation of maintenance dialysis or receipt of a kidney transplant

For further information on chronic kidney disease or cardio-renal-metabolic conditions, visit: www.boehringer-ingelheim.com/chronic-kidney-disease

About EMPA-KIDNEY: The study of heart and kidney protection with empagliflozin^1,2,8

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, kidney death, or a sustained decline of ≥40 percent in eGFR from randomization. Key secondary outcomes include cardiovascular death or hospitalization for heart failure, all-cause hospitalization, and all-cause mortality. EMPA-KIDNEY includes 6,609 adults randomized from eight countries 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 Population Health Research Unit (MRC 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 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.

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

References:

1. EMPA-KIDNEY full data presentation, presented on 4 November 2022 at the American Society of Nephrology (ASN) Congress 2022 - Kidney Week.
2. Herrington, W.G. et al. Empagliflozin in Patients with Chronic Kidney Disease, N Engl J Med, online publication on November 4, 2022, at NEJM.org. DOI: 10.1056/NEJMoa2204233.
3. Iwagami M, Caplin B, Smeet L, et al. Chronic kidney disease and cause-specific hospitalisation: a matched cohort study using primary and secondary care patient data. British Journal of General Practice. 2018; 68(673): e512-e523.
4. USRDS. 2021 Annual Report. [online] Last accessed: October 2022.
5. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2020; 395:709-23.
6. Nichols GA, Ustyugova A, Déruaz-Luyet A, et al. Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart Failure. JASN. 2020; 31 (7):1594-1601. 
7. The EMPA-KIDNEY Collaborative Group. [Published online ahead of print March 3, 2022]. Nephrol Dial Transplant. 2022. DOI:10.1093/ndt/gfac040. 
8. Clinical Trials. EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin). Available at: https://clinicaltrials.gov/ct2/show/NCT03594110 Last accessed: October 2022.