Ingelheim, Germany and Indianapolis, US, 6 July 2021 – The EMPEROR-Preserved Phase III trial met its primary endpoint, establishing empagliflozin as the first and only therapy to significantly reduce the risk of the composite of cardiovascular death or hospitalization for heart failure in adults, with or without diabetes, who live with heart failure with preserved ejection fraction (HFpEF). Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced the topline results today. When added to the EMPEROR-Reduced trial results, these findings demonstrate empagliflozin’s efficacy in all forms of heart failure regardless of ejection fraction. The safety profile was generally consistent with the known safety profile of empagliflozin.
“We look forward to presenting the EMPEROR-Preserved results at ESC 2021, which should offer a breakthrough in cardiovascular medicine and a new hope for people with HFpEF, which is an increasingly prevalent public health issue. HFpEF has long been the most challenging form of heart failure to treat,” said Professor Stefan Anker, Heart Failure Cardiologist at Charité Berlin, Germany, and EMPEROR-Preserved Principal Investigator. “Building on previous results from the EMPA-REG-OUTCOME trial, and the EMPEROR-Reduced trial in heart failure with reduced ejection fraction, the EMPEROR-Preserved findings demonstrate that empagliflozin reduces cardiovascular death or hospitalization for heart failure and has the potential to transform the care of people living with heart failure.”
Heart failure poses a significant global disease burden: more than 60 million patients worldwide have heart failure and half of them have HFpEF.3,4 Heart failure is a leading cause of hospitalization and is becoming increasingly prevalent in Western countries due to aging populations.3 The risk of death in people with heart failure rises with each hospital admission.5 Heart failure with left ventricular preserved ejection fraction occurs when the left ventricle of the heart is unable to fill properly, resulting in less blood being pumped to the body.6
“The totality of evidence from the trial points to the potential of empagliflozin to redefine treatment of heart failure with preserved ejection fraction, which affects approximately 30 million people worldwide,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “Until now, there have been no clinical studies demonstrating reduced risk of heart failure hospitalizations or cardiovascular mortality for all adults with this prevalent and life-limiting condition. With the earlier EMPEROR-Reduced trial results, we are confident in the potential of empagliflozin to positively impact the lives of adults across the full spectrum of heart failure.”
“Empagliflozin was the first SGLT2 inhibitor to reduce cardiovascular death for people with type 2 diabetes and cardiovascular disease, and we have now reached another important milestone, this time in heart failure,” added Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. “The EMPEROR-Preserved topline results offer promise in a type of heart failure that until now has traditionally been very challenging to treat effectively. The EMPEROR heart failure studies are part of our EMPOWER clinical trial program exploring the effect of empagliflozin across a spectrum of cardio-renal-metabolic diseases, aiming to significantly improve outcomes in these highly prevalent conditions that impact many people’s lives.”
The EMPEROR-Preserved trial investigated empagliflozin 10 mg compared to placebo.7 Full results from the EMPEROR-Preserved trial are scheduled for presentation at the European Society of Cardiology (ESC) Congress 2021 on 27 August. Boehringer Ingelheim and Lilly plan for regulatory submissions in 2021. These results add to previous findings from the EMPEROR-Reduced Phase III trial, which showed that empagliflozin significantly reduced the combined relative risk of cardiovascular death or hospitalization for heart failure by 25 percent, compared to placebo in adults with heart failure with reduced ejection fraction (HFrEF).8
About the EMPEROR heart failure studies7, 9
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
Ejection fraction is a measurement of the percentage of blood the left ventricle pumps out with each contraction.10 When the heart relaxes, the ventricle refills with blood.
About the EMPOWER program
The Boehringer Ingelheim and Lilly 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.11 Through the EMPOWER program, the Alliance is working to advance knowledge of these interconnected systems and create care which offers integrated, multi-organ benefits. Comprised of nine clinical trials and a real-world evidence study, 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 or to do so requires increased blood volume leading to fluid accumulation (congestion) in the lungs and peripheral tissues.12 It is a common condition affecting over 60 million people worldwide and expected to increase as the population ages.3,4 Heart failure is highly prevalent in people with diabetes;13 however, approximately half of all people with heart failure do not have diabetes.14
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.4
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.15,16,17
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.18,19,20
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 172209
Greg Kueterman
Senior Director of Communications
Eli Lilly and Company
Phone: +1 317 432 5195
References
1 Butler J, Fonarow G, Zile M, et al. Developing therapies for heart failure with preserved ejection fraction: Current State and Future Directions. JACC Heart Fail. 2014 Apr;2(2):97–112.
2 Shah SJ, Borlaug B, Kitzman D, et al. Research priorities for heart failure with preserved ejection fraction. Circulation. 2020;141:1001–26.
3 Andersen MJ, Borlaug BA. Heart failure with preserved ejection fraction: current understandings and challenges. Curr Cardiol Rep. 2014 Jul;16(7):501.
4 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.
5 Solomon S, Dobson J, Pocock S, et al. Influence of Nonfatal Hospitalization for Heart Failure on Subsequent Mortality in Patients With Chronic Heart Failure. Circulation. 2007;116(13):1482–7.
6 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: July 2021
7 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: July 2021.
8 Packer M, Anker SD, Butler J, et al. Cardiac and Renal Outcomes With Empagliflozin in Heart Failure With a Reduced Ejection Fraction. N Engl J Med. 2020;383:1413–24.
9 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: July 2021.
10 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: July 2021.
11 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.
12 American Heart Association. What is Heart Failure? Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure. Accessed: July 2021.
13 Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121–41.
14 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.
15 García-Donaire JA, Ruilope LM. Cardiovascular and Renal Links along the Cardiorenal Continuum. Int J Nephrol. 2011;2011:975782.
16 Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246–58.
17 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.
18 Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed: July 2021.
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. Accessed July 2021.
20 Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.
