Health Canada issues Notice of Compliance (NOC) for Jardiance® (empagliflozin) for the treatment of heart failure with reduced ejection fraction

Burlington, ON and Toronto, ON – November 2, 2021 – Boehringer Ingelheim (Canada) Ltd and Eli Lilly Canada Inc. are pleased to announce that Jardiance® (empagliflozin) has been granted marketing authorization by Health Canada as a treatment for heart failure with reduced ejection fraction (HFrEF), as an adjunct to standard of care therapy, in adults with an eGFR as low as 20 mL/min/1.73 m².³ The extension of the indication follows marketing authorization granted by Health Canada in 2015 for the treatment of adults with insufficiently controlled type 2 diabetes mellitus; and in 2016, as an add-on combination to reduce the incidence of cardiovascular death in patients with type 2 diabetes mellitus and established cardiovascular disease.³

“When we look at healthcare expenditures for heart failure in Canada, it is hospitalization that makes up the bulk of the attributable expenses for care. With empagliflozin now approved by Health Canada for heart failure with reduced ejection fraction, we can look forward to reducing the risk of hospitalization,” says Dr. Shelley Zieroth, Cardiologist and Director at Winnipeg’s St. Boniface Hospital Heart Failure and Transplant Clinics and Professor in the College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba. “The availability of a new heart failure treatment is a major step forward in improving the standard of care for heart failure patients and is definitely worth celebrating.”

The marketing authorization is based on results from the EMPEROR-Reduced trial in which empagliflozin showed a significant 25 per cent reduction in the combined relative risk versus placebo of cardiovascular death or hospitalization due to heart failure.¹ The findings from the primary endpoint were consistent in subgroups with or without type 2 diabetes. Key secondary endpoints were also significantly improved with empagliflozin, including a 30 per cent reduction in the relative risk of first and recurrent hospitalization for heart failure.¹  

Heart failure affects more than 60 million people worldwide.⁴ In Canada, nearly 670,000 Canadians are currently living with heart failure and close to 93,000 new cases are diagnosed each year.²

“Jardiance was the first SGLT2 inhibitor to demonstrate cardiovascular protective effects and improve cardiovascular outcomes in patients with type 2 diabetes,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “We are delighted to now be able to offer Jardiance to people with heart failure with reduced ejection fraction in Canada, regardless of diabetes status.”

“The introduction of empagliflozin for this type of heart failure in Canada is a significant milestone for the Boehringer Ingelheim and Lilly Alliance,” continued Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. “We are committed to finding solutions for the millions of people who live with heart failure and important metabolic conditions around the world.”

Heart failure is frequently associated with other diseases of the cardio-renal-metabolic systems such as type 2 diabetes and kidney disease. Due to the interconnected nature of these systems, improvement in one system can lead to positive effects throughout the others. Heart failure is a condition in which the heart cannot pump sufficient blood to the rest of the body.⁵ There are two forms of the condition; heart failure with reduced ejection fraction (HFrEF) means the heart cannot contract normally, while preserved ejection fraction means the heart cannot properly fill with blood. People with heart failure often experience breathlessness and fatigue, which can severely impact their quality of life.^6,7

The EMPEROR-Reduced trial is part of the EMPOWER clinical program, the broadest and most comprehensive of any SGLT2 inhibitor, exploring the impact of empagliflozin on the lives of people across the spectrum of cardio-renal-metabolic conditions.

About the EMPEROR Heart Failure Studies^8,9
The EMPEROR (Empagliflozin outcome trial in patients with chronic heart failure) heart failure studies are two Phase III, randomized, double-blind trials investigating once-daily empagliflozin compared with placebo in adults with heart failure with preserved or reduced ejection fraction, with or without diabetes, who are receiving current standard of care:

• EMPEROR-Reduced [NCT03057977] investigated the safety and efficacy of empagliflozin in patients with chronic heart failure with reduced ejection fraction (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 heart failure with preserved ejection fraction (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

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.¹⁰ 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 eight 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 studied worldwide in clinical studies, it is the broadest and most comprehensive clinical program 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.^5,11 It is a common condition affecting over 60 million people worldwide and expected to increase as the population ages.^4,12 In Canada, nearly 670,000 people are living with heart failure.² Heart failure is twice as common in people with diabetes.¹³  

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.¹⁴ 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.¹⁴ 
• 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.¹⁴   

People with heart failure often experience shortness of breath and fatigue, which can severely impact their quality of life.⁷ Individuals with heart failure often also have impaired kidney function, which can further worsen patient outcomes and quality of life.¹⁵ 

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.^4,10

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. It was the first type 2 diabetes medicine to include in its label in several countries cardiovascular death risk reduction data in patients with type 2 diabetes and established cardiovascular disease.^16,17,18,3

Empagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes and as an adjunct to diet, exercise and standard care therapy to reduce the incidence of cardiovascular death in patients with type 2 diabetes mellitus and established cardiovascular disease.^16,17,18,3 Additionally, empagliflozin is approved for the treatment of adults with HFrEF in the European Union and the U.S.^16,19 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.²⁰ Empagliflozin is also currently being investigated in chronic kidney disease.²¹ 

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. 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):1789–1858.

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

3. American Heart Association. Warning Signs of Heart Failure. Available at: https://www.heart.org/en/health-topics/heart-failure/warning-signs-of-heart-failure. Accessed June 2021.

4. 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.

5. 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 June 2021.

6. 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 June 2021.

7. 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. The Lancet. 2016; 388(10053):1459–544.

8. 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.

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

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

11. 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.

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

13. 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.

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

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

16. 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: October 2021

17. 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.

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