INGELHEIM, Germany & INDIANAPOLIS--(BUSINESS WIRE)--Full results from the landmark EMPEROR-Preserved Phase III trial demonstrated that empagliflozin showed an impressive 21 percent 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.¹?The benefit was independent of ejection fraction or diabetes status,^1?establishing empagliflozin as the first and only treatment to significantly improve outcomes for the full spectrum of heart failure patients. The results were presented today at the European Society of Cardiology (ESC) Congress 2021^2?and published in?The New England Journal of Medicine,^1?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 percent and significantly slowed kidney function decline.¹ ?For people with heart failure with preserved ejection fraction, the reality is that so far there are no clinically proven treatments we can offer that would make a significant impact on their condition,? said Professor Stefan Anker, EMPEROR-Preserved Principal Investigator and Heart Failure Cardiologist at Charit? Berlin, Germany. ?This data brings hope for millions of patients suffering from heart failure with a preserved ejection fraction. The primary endpoint was similarly improved in all subgroups of patients, in men and women, with and without diabetes, and regardless of their ejection fraction and kidney function level. This underlines the breadth of empagliflozin?s efficacy and its potential overall impact.? More than 60 million people worldwide have heart failure and approximately half of them have HFpEF, which is also known as diastolic heart failure.^3,4?HFpEF has been described as the single largest unmet need in cardiovascular medicine based on prevalence, poor outcomes and the absence of clinically proven therapies to date.^5,6 EMPEROR-Preserved included 5,988 people with heart failure.¹?Of these, 4,005 had a left ventricular ejection fraction (LVEF) of 50 percent or above and 1,983 had a LVEF below 50 percent.¹?Trial participants were randomly assigned to empagliflozin 10 mg (n=2,997) or placebo (n=2,991) once daily.^1?The overall safety data was consistent with previous findings, confirming the well-established safety profile of empagliflozin.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.? The benefits demonstrated in the EMPEROR-Preserved trial are similar to those in the EMPEROR-Reduced trial, in which empagliflozin significantly reduced the relative risk of the composite endpoint of cardiovascular death or hospitalization for heart failure by 25 percent, compared with placebo, in adults with heart failure with reduced ejection fraction (HFrEF).⁸?Together, these studies demonstrate the benefits of empagliflozin for patients across the full heart failure spectrum. Empagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes.^9,10,11?Additionally, empagliflozin is approved for the treatment of adults with HFrEF in the European Union and the U.S.^9,12?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.¹³?Empagliflozin is also currently being investigated in chronic kidney disease.¹⁴

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About the EMPEROR heart failure studies^15,16 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 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.¹⁷?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 progressive, debilitating and potentially fatal condition that occurs when the heart cannot supply adequate circulation to meet the body?s demands for oxygenated blood.¹⁸?To do so, it requires increased blood volume leading to fluid accumulation (congestion) in the lungs and peripheral tissues.¹⁹?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;²⁰?however, more than half of all people with heart failure do not have diabetes.²¹ 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.^22?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.²²
• 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.²²

People with heart failure often experience breathlessness and fatigue, which can severely impact their quality of life.^23?Individuals with heart failure often also have impaired kidney function, which can have a significant negative impact on prognosis.²⁴ 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.^4,17 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.^25,26,27 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.^9,10,11 Please click on the following link for ?Notes to Editors? and ?References??https://www.boehringer-ingelheim.com/press-release/emperor-preserved-heart-failure-full-data