Ingelheim, Germany and Indianapolis, U.S., 6 November 2021 – Empagliflozin reduced the risk for the composite primary endpoint of cardiovascular death or hospitalization for heart failure and slowed kidney function decline in adults with heart failure with left ventricular ejection fraction (LVEF) over 40 percent regardless of chronic kidney disease status at baseline, according to findings from a new prespecified sub-analysis of the EMPEROR-Preserved® Phase III trial.1 In EMPEROR-Preserved®, two thirds of enrolled adults had heart failure with preserved ejection fraction (HFpEF; LVEF of at least 50 percent) and one third had mildly reduced LVEF (greater than 40 percent but less than 50 percent).2 The results were presented today at the American Society of Nephrology Kidney Week 2021, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.1
“Heart failure and chronic kidney disease are intimately linked — the risk of death in people with heart failure increases with kidney function decline,” said Faiez Zannad, M.D., Ph.D., EMPEROR Program Clinical Investigator and Emeritus Professor of Therapeutics and Cardiology at the University of Lorraine, France. “The consistent benefits shown for the reduction of serious heart failure events and the slowing of kidney function decline regardless of chronic kidney disease status are welcome results for both patients and physicians. The findings underscore the potential value of empagliflozin across a wide range of kidney function in this heart failure population that includes people with preserved ejection fraction.”
Nearly half of adults with heart failure also have chronic kidney disease.3 Together, these conditions are associated with high mortality rates and risk for hospital admission.3 More than 60 million people worldwide have heart failure, and approximately half of them have HFpEF.4,5 No currently approved treatments have been clinically proven to significantly improve outcomes across the full spectrum of heart failure.
“In those living with heart failure, including those with preserved ejection fraction, chronic kidney disease poses an additional challenge to managing these patients and contributes to the worsening and progression of heart failure,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “It is very encouraging to see the evidence from EMPEROR-Preserved®, which shows cardiovascular and kidney benefits in these patients with heart failure, including those with HFpEF, and concomitant chronic kidney disease.”
As previously reported, EMPEROR-Preserved® showed that empagliflozin significantly reduced the risk for the composite primary endpoint of cardiovascular death or hospitalization for heart failure in adults with heart failure with LVEF over 40 percent compared with placebo.2 Empagliflozin also significantly reduced the risk of first and recurrent hospitalizations for heart failure and slowed kidney function decline.2
Over half (53.5 percent) of adults in EMPEROR-Preserved® had chronic kidney disease (defined as eGFR below 60 mL/min/1.73 m2 or UACR above 300 mg/g) at trial entry, and 9.7 percent had severe kidney impairment (eGFR below 30 mL/min/1.73 m2).1 The new prespecified sub-analysis of EMPEROR-Preserved® demonstrated that the benefits seen in the overall population were consistent in adults with and without chronic kidney disease.1 Empagliflozin consistently improved cardiovascular outcomes and slowed kidney function decline across the full range of kidney function down to an eGFR of 20 mL/min/1.73 m2.1 Empagliflozin was well tolerated regardless of the level of baseline kidney function.1
“This data marks an important milestone for the growing number of people living with both heart failure and chronic kidney disease, many of whom are in need of additional treatment options for these interconnected, complex conditions,” said Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. “We look forward to continuing research with the goal of addressing the unmet needs of those with kidney impairment, including through our EMPA-KIDNEY Phase III trial of empagliflozin, from which we eagerly await a readout next year.”
Empagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes.6,7,8 Additionally, empagliflozin is approved for the treatment of adults with heart failure with reduced ejection fraction in the European Union and the U.S..6,7 Boehringer Ingelheim and Lilly Alliance plan for global regulatory submissions in HFpEF in 2021. Research is ongoing regarding the effects of empagliflozin on hospitalization for heart failure and mortality in post-myocardial infarction (heart attack) patients with high risk of heart failure.9 Empagliflozin is also currently being investigated in chronic kidney disease.10
About the EMPEROR heart failure studies11,12
The EMPEROR (EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure) chronic heart failure studies were two Phase III, randomized, double-blind trials that investigated once-daily empagliflozin compared to placebo in adults with chronic HFrEF or HFpEF, with or without diabetes:
- EMPEROR-Reduced® [NCT03057977] investigated the safety and efficacy of empagliflozin in patients with chronic HFrEF.
- Primary endpoint: time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure
- Number of patients: 3,730
- Completion: 2020
- EMPEROR-Preserved® [NCT03057951] investigated the safety and efficacy of empagliflozin in patients with chronic HFpEF.
- Primary endpoint: time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure
- Number of patients: 5,988
- Completion: 2021
- Link to lay summary
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.13 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 one of the broadest and most comprehensive clinical programs for an SGLT2 inhibitor to date.
About heart failure
Heart failure is a progressive, debilitating and potentially fatal condition that occurs when the heart cannot supply adequate circulation to meet the body’s demands for oxygenated blood.14 To do so, it requires increased blood volume leading to fluid accumulation (congestion) in the lungs and peripheral tissues.15 It is a common condition affecting over 60 million people worldwide and expected to increase as the population ages.4,5 Heart failure is highly prevalent in people with diabetes;16 however, more than half of all people with heart failure do not have diabetes.17
There are different types of heart failure. People with left-sided heart failure have either a reduced or a preserved ejection fraction. Ejection fraction is a measurement of the percentage of blood the left ventricle pumps out with each contraction.18 When the heart relaxes, the ventricle refills with blood.
- Heart failure with preserved ejection fraction occurs when the left ventricle of the heart is unable to relax and properly fill with blood, resulting in less blood being available to be pumped out to the body.18
- Heart failure with reduced ejection fraction occurs when the left ventricle of the heart is not able to contract effectively, which means that the heart cannot pump with enough force, so less blood is pushed out to the body.18
People with heart failure often experience breathlessness and fatigue, which can severely impact their quality of life.19 Individuals with heart failure often also have impaired kidney function, which can have a significant negative impact on prognosis.20
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.5,13
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.21,22,23
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.6,7,8
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 chronic kidney disease.
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 clinical trials to evaluate empagliflozin as a treatment for adults with heart failure 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:
Stefanie Molkenthin
Product Communication Manager
Boehringer Ingelheim
Phone: +49 (6132) 77 172 209
Stephan Thalen
Global Business Communications
Eli Lilly and Company
Phone: (317) 276-8304
References
1 Zannad F. EMPEROR-Preserved: Empagliflozin and Outcomes in Heart Failure with a Preserved Ejection Fraction and CKD. Presented on 5 November 2021 at the American Society of Nephrology (ASN) Kidney Week 2021.
2 Anker S, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385:1451–61.
3 Banerjee D, Wang AY. Personalizing heart failure management in chronic kidney disease patients. Nephrol Dial Transplant. 2021;doi:10.1093/ndt/gfab026.
4 Andersen MJ, Borlaug BA. Heart failure with preserved ejection fraction: current understandings and challenges. Curr Cardiol Rep. 2014;16(7):501.
5 GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.
6 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. Accessed: November 2021.
7 Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed: November 2021.
8 Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.
9 ClinicalTrials.gov. EMPACT-MI: A Study to Test Whether Empagliflozin Can Lower the Risk of Heart Failure and Death in People Who Had a Heart Attack (Myocardial Infarction). Available at: https://clinicaltrials.gov/ct2/show/NCT04509674. Accessed: November 2021.
10 ClinicalTrials.gov. EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03594110. Accessed: November 2021.
11 ClinicalTrials.gov. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced). Available at: https://clinicaltrials.gov/ct2/show/NCT03057977. Accessed: November 2021.
12 ClinicalTrials.gov. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved). Available at: https://clinicaltrials.gov/ct2/show/NCT03057951. Accessed: November 2021.
13 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.
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15 American Heart Association. Types of Heart Failure. Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/types-of-heart-failure. Accessed: November 2021.
16 Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121–41.
17 Dunlay SM, Givertz MM, Aguilar D, et al. Type 2 Diabetes Mellitus and Heart Failure: A Scientific Statement From the American Heart Association and the Heart Failure Society of America. Circulation. 2019;140:e294–e324.
18 American Heart Association. Ejection Fraction Heart Failure Measurement. Available at: https://www.heart.org/en/health-topics/heart-failure/diagnosing-heart-failure/ejection-fraction-heart-failure-measurement. Accessed: November 2021.
19 Calvert MJ, Freemantle N, Cleland JGF. The impact of chronic heart failure on health‐related quality of life data acquired in the baseline phase of the CARE‐HF study. Eur J Heart Fail. 2005;7(2):243–51.
20 Sarnak MJ. A patient with heart failure and worsening kidney function. Clin J Am Soc Nephrol. 2014;9(10):1790–98.
21 García-Donaire JA, Ruilope LM. Cardiovascular and Renal Links along the Cardiorenal Continuum. Int J Nephrol. 2011;2011:975782.
22 Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246–58.
23 Thomas M, Cooper M, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2015;12:73–81.
