Jardiance® (empagliflozin) becomes the first and only approved treatment in Europe for adults with symptomatic chronic heart failure regardless of ejection fraction

Ingelheim, Germany, 07 March 2022 – The European Commission (EC) has granted marketing authorization for Jardiance® (empagliflozin) as a treatment for adults with symptomatic chronic heart failure, Boehringer Ingelheim and Eli Lilly and Company have announced.¹ The landmark approval makes Jardiance® the first and only approved treatment for all adults with symptomatic chronic heart failure, which includes patients across the full spectrum of LVEF, including both heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF).

Heart failure affects more than 15 million people in Europe and causes almost 2 million hospital admissions yearly.²  Approximately half of these patients have HFpEF,³ which has been described as the single largest unmet need in cardiovascular medicine based on prevalence, poor outcomes and the absence of treatment options until now.^4,5

“It’s estimated that over 60 million people worldwide are living with heart failure. This complex medical condition very often has a devastating impact on quality of life: physically, emotionally and even financially for those who can no longer work,” said Neil Johnson, Executive Director of the Global Heart Hub. “New treatments for a heretofore underserved population of patients which can improve outcomes and reduce hospital admissions is just great news for patients. The impact of new and emerging treatments on quality of life, from a patient and carer perspective, cannot be overstated because they provide hope and comfort in the knowledge that heart failure can be treated. This in turn has an enormously positive impact on overall mental health and wellbeing by decreasing anxiety, stress and worry.”

The approval is based on results from the breakthrough EMPEROR-Preserved® Phase III trial, which investigated the effect of empagliflozin 10 mg compared with placebo once daily, both added to the standard of care, in 5,988 adults with heart failure with LVEF over 40%.⁶ In the trial, empagliflozin demonstrated a 21% relative risk reduction (3.3% absolute risk reduction, 0.79 HR, 0.69-0.90 95% CI) for the composite primary endpoint of cardiovascular death or hospitalization for heart failure. Established benefit was regardless of ejection fraction or diabetes status.⁶ Empagliflozin was previously approved for the treatment of adults with symptomatic chronic HFrEF.

“The European approval will redefine the standard of care for millions of people in the EU living with heart failure,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “We are writing history as the first and only approved treatment to show significant clinical benefits for adults with heart failure across the range of left ventricular ejection fraction. This approval reinforces empagliflozin's potential to transform the lives of adults with chronic heart failure and builds on Boehringer Ingelheim and Lilly's legacy of leadership in this space.”

“We are delighted with the EC decision to approve empagliflozin as the first and only treatment for adults with symptomatic chronic heart failure, following our recent U.S. FDA approval,” said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Lilly. “This is an essential step forward in our efforts to advance treatment options for people with a range of cardio-renal-metabolic conditions. We continue to explore empagliflozin’s ability to improve outcomes across these conditions and look forward to the upcoming results from the EMPA-KIDNEY trial, which explores the potential of empagliflozin in treating chronic kidney disease.”

The EMPEROR-Preserved 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 clinical trials^7,8
The EMPEROR (EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure) chronic heart failure trials 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.
  o    Primary endpoint: time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure
  o    Number of patients: 3,730
  o    Completion: 2020
   
• EMPEROR-Preserved [NCT03057951] investigated the safety and efficacy of empagliflozin in patients with chronic HFpEF.
  o    Primary endpoint: time to first event of adjudicated cardiovascular death or adjudicated hospitalization for heart failure 
  o    Number of patients: 5,988
  o    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.⁹ 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 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 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.^10,11 It is a widespread condition affecting over 15 million people in Europe² and over 60 million people worldwide and expected to increase as the population ages.^12,13 Heart failure is highly prevalent in people with diabetes; 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.

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

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 Jardiance as a treatment for adults with type 2 diabetes, to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease, and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, and as a potential treatment for adults with cardio-renal-metabolic conditions and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date or that Jardiance will receive additional regulatory approvals. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, please see Lilly's most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

CONTACTS:

Stefanie Molkenthin
Boehringer Ingelheim 
Email: press@boehringer-ingelheim.com    
Phone: +49 (6132) 77 172 209

Stephan Thalen 
Eli Lilly and Company
Email: stephan.thalen@lilly.com
Phone: (317) 903-5640

References
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2  Health Policy Partnership. Heart failure policy and practice in Europe. Available at: https://www.healthpolicypartnership.com/app/uploads/Heart-failure-policy-and-practice-in-Europe.pdf. Last accessed: March 2022.
3  Andersen MJ, Borlaug BA. Heart failure with preserved ejection fraction: current understandings and challenges. Curr Cardiol Rep. 2014 Jul;16(7):501.
4  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.
5  Shah SJ, Borlaug B, Kitzman D, et al. Research priorities for heart failure with preserved ejection fraction. Circulation. 2020;141:1001–26. 
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8  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. Last accessed: March 2022.
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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.
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19  Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Last accessed: March 2022.