New empagliflozin data shows statistically significant improvement in heart failure outcomes in adults with preserved ejection fraction

Burlington, ON and Toronto, ON – August 30, 2021 – Full results from the landmark EMPEROR-Preserved Phase III trial demonstrated that empagliflozin showed a 21 per cent relative risk reduction for the composite primary endpoint of cardiovascular death or hospitalization for heart failure in adults with heart failure with preserved ejection fraction (HFpEF) compared with placebo.² The benefit was independent of ejection fraction or diabetes status,² establishing empagliflozin as the first and only treatment to significantly improve outcomes for the full spectrum of heart failure patients. The results were presented on August 27, at the European Society of Cardiology (ESC) Congress 2021¹ and published in The New England Journal of Medicine,² Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.

Key secondary endpoint analyses from the trial showed that empagliflozin also reduced the relative risk of first and recurrent hospitalizations for heart failure by 27 per cent and significantly slowed kidney function decline.²

“Until now, there have been no clinically proven treatment options for patients who have heart failure with a preserved ejection fraction,” said Dr. Shelley Zieroth, cardiologist and director of St. Boniface Hospital Heart Failure and Transplant Clinics, in Winnipeg, MB, and a clinical investigator for the EMPEROR-Preserved trial. “Results from the study show that empagliflozin is effective in not only treating heart failure with preserved ejection fraction, but also keeping patients out of hospital and slowing kidney decline – which are key factors for prolonging life and allowing my patients to continue to live well. These findings not only give me hope as a clinician but for my patients who at present have limited options available to them.”

Heart failure affects more than 60 million people worldwide.⁴ In Canada, approximately 670,000 Canadians are currently living with heart failure and nearly 93,000 new cases are diagnosed each year.³ HFpEF, which is also known as diastolic heart failure, comprises half of all heart failure cases.⁵ HFpEF has been described as the single largest unmet need in cardiovascular medicine based on its prevalence, high morbidity and mortality, and the absence of clinically proven therapies to date.^6,7

“Heart failure is a complex, serious health issue and a leading cause of hospitalization,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “The risk of death in people with heart failure rises with each hospital admission and with kidney function decline. The landmark EMPEROR-Preserved trial shows that empagliflozin brings significant benefit, which is incredibly exciting and welcome news for both the medical and patient communities.”

“These impressive results will bring hope for the millions of people who currently have limited therapeutic options for a very serious, life-threatening condition,” said Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. “Now there is a light at the end of the tunnel. If approved, empagliflozin would become the first clinically proven therapy across the full heart failure spectrum. The results of EMPEROR-Preserved offer an opportunity to fundamentally change the future for people with heart failure.” 

EMPEROR-Preserved included 5,988 people with heart failure.² Of these, 4,005 had a left ventricular ejection fraction (LVEF) of 50 per cent or above and 1,983 had a LVEF between 40 and 50 per cent.² Trial participants were randomly assigned to empagliflozin 10 mg (n=2,997) or placebo (n=2,991) once daily.² The overall safety data was consistent with previous findings, confirming the well-established safety profile of empagliflozin.⁸

The benefits demonstrated in the EMPEROR-Preserved trial are similar to those in the EMPEROR-Reduced trial, where empagliflozin significantly reduced the relative risk of the composite endpoint of cardiovascular death or hospitalization for heart failure by 25 per cent, compared with placebo, in adults with heart failure with reduced ejection fraction (HFrEF).⁹ Together, these studies demonstrate the benefits of empagliflozin for patients across the full heart failure spectrum.

About the EMPEROR heart failure studies ^10,11
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; which included 36 study sites in Canada
  • 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; which included 34 study sites in Canada
  • Completion: 2021
  • Link to lay summary
     

About the EMPOWER program
The Boehringer Ingelheim and Lilly Diabetes 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.¹²

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 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 studies, it is one of the broadest and most comprehensive clinical programs for an SGLT2 inhibitor to date. 
 

About heart failure
Heart failure is a serious condition, that occurs when the heart cannot keep up with its workload, and the body may not get the oxygen that it needs. As the left and right sides of the heart fail, fluid may build up in the lungs, abdomen, or legs.^13,14 It is a common condition affecting over 60 million people worldwide and expected to increase as the population ages.^4,5 In Canada, approximately 670,000 people are living with heart failure.³ Heart failure is twice as common in people with diabetes.¹⁵

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.¹⁶ 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.¹⁶
• 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.¹⁶

People with heart failure often experience shortness of breath and fatigue, which can severely impact their quality of life.¹⁷ Individuals with heart failure often also have impaired kidney function, which can further worsen patient outcomes and quality of life.¹⁸

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.^4,12

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.^19,20,21,22

Empagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes.^19,20,21 Additionally, empagliflozin is approved for the treatment of adults with HFrEF in the European Union and the U.S.^19,23 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. ²⁴ Empagliflozin is also currently being investigated in chronic kidney disease.²⁵

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 (Canada) Ltd.
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. Approximately 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health and Biopharmaceutical Contract Manufacturing. The Canadian headquarters of Boehringer Ingelheim was established in 1972 in Montreal, Quebec and is now located in Burlington, Ontario. Boehringer Ingelheim employs approximately 600 people across Canada. Learn more at www.boehringer-ingelheim.ca.
 

About Eli Lilly Canada
Eli Lilly and Company is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by Colonel Eli Lilly, who was committed to creating high quality medicines that meet people's needs, and today we remain true to that mission in all our work. Lilly employees work to discover and bring life-changing medicines to people who need them, improve the understanding and management of disease, and contribute to our communities through philanthropy and volunteerism.

Eli Lilly Canada was established in 1938, the result of a research collaboration with scientists at the University of Toronto, which eventually produced the world's first commercially available insulin. Our work focuses on oncology, diabetes, autoimmunity, neurodegeneration, and pain. To learn more about Lilly Canada, please visit us at www.lilly.ca.

For our perspective on issues in healthcare and innovation, follow us on twitter @LillyPadCA and @LillyMedicalCA.

References

1. Anker S. EMPEROR-Preserved: effect of empagliflozin on cardiovascular death and heart failure hospitalisations in patients with heart failure with a preserved ejection fraction, with and without diabetes. Presented on 27 August 2021 at the European Society of Cardiology (ESC) Congress 2021 – The Digital Experience.

2. Anker S, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021; 10.1056/NEJMoa2107038.

3. Public Health Agency of Canada. Heart Disease in Canada. Available at: https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/diseases-conditions/heart-disease-fact-sheet/heart-disease-factsheet-eng.pdf. Accessed: August 2021. 

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. Andersen MJ, Borlaug BA. Heart failure with preserved ejection fraction: current understandings and challenges. Curr Cardiol Rep. 2014;16(7):501.

6. 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.

7. Shah SJ, Borlaug B, Kitzman D, et al. Research priorities for heart failure with preserved ejection fraction. Circulation. 2020;141:1001–26.

8. Boehringer Ingelheim. Data on file.

9. 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.

10. 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: August 2021.

11. 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: August 2021.

12. 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.

13. American Heart Association. What is Heart Failure? Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure. Accessed: August 2021.

14. 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: August 2021.

15. Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121–41.

16. 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: August 2021.

17. 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.

18. Sarnak MJ. A patient with heart failure and worsening kidney function. Clin J Am Soc Nephrol. 2014;9(10):1790–98.

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: August 2021.

20. Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed: August 2021.

21. Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.

22. Product Monograph Jardiance®. Canada. Available at: https://www.boehringer-ingelheim.ca/sites/ca/files/documents/jardiancepmen.pdf. Accessed: August 2021.

23. Boehringer Ingelheim. Press release. US FDA approves Jardiance® (empagliflozin) to treat adults living with heart failure with reduced ejection fraction. Available at: https://www.boehringer-ingelheim.us/press-release/us-fda-approves-jardiance-empagliflozin-treat-adults-living-heart-failure-reduced. Accessed: August 2021. 

24. 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: August 2021.

25. ClinicalTrials.gov. EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03594110