Empagliflozin (Jardiance®) meets primary endpoint in Phase III heart failure trial with and without diabetes

• Empagliflozin (10 mg) (Jardiance^®)^1,2 significantly reduced the risk of cardiovascular death or hospitalisation for heart failure versus placebo on top of guideline-directed medical therapy in adults with heart failure with reduced ejection fraction, meeting the EMPEROR-Reduced trial primary endpoint
• The study included patients with and without type 2 diabetes
• Survival of heart failure in the UK still lags behind other serious conditions like cancer and has only shown modest improvement in recent years³
• There remains an unmet need in the treatment of heart failure with over half of those diagnosed in the UK dying within five years⁴
• The true burden of heart failure in Ireland is still not fully understood and the recorded number of deaths attributed to heart failure may be underestimated⁵

Bracknell and Basingstoke, UK – Positive top-line results from the EMPEROR-Reduced Phase III trial in adults with heart failure with reduced ejection fraction (HFrEF), with and without type 2 diabetes, were announced today by Boehringer Ingelheim and Eli Lilly and Company. EMPEROR-Reduced met its primary endpoint, demonstrating superiority with empagliflozin (10mg)^1,2 compared to placebo in reducing the risk for the composite of cardiovascular death or hospitalisation due to heart failure, when added on top of guideline-directed medical therapy. Overall, the safety profile was similar to the known safety profile of empagliflozin.

“Heart failure is a common, but very serious chronic cardiovascular disorder, and it causes substantial disability while threatening the lives of millions of people worldwide,” said Milton Packer, M.D., Chair of the Executive Committee for the EMPEROR Program and Distinguished Scholar in Cardiovascular Science at Baylor University Medical Center in Dallas, Texas, US. “The results of the EMPEROR-Reduced trial indicate that SGLT2 inhibitors have the potential to become new standard of care for this disease, which will be a meaningful addition to the currently established treatments.”

In the UK and Ireland, heart failure is the most common cause of hospital admission in people aged over 65.^6,7 It is also the leading cause of hospitalisation in the US and Europe.⁸ The risk of death in people with heart failure rises with each hospital admission.⁹ Heart failure with reduced ejection fraction occurs when the heart muscle does not contract effectively, and less blood is pumped out to the body compared to a normally functioning heart.¹⁰ Symptoms associated with heart failure, such as breathlessness and fatigue, can impact quality of life.¹¹

“With over one million people living with heart failure today in the UK and Ireland, and around 200,000 new cases diagnosed each year in the UK alone, it is becoming increasingly important that new treatment options are explored,” said Professor Iain Squire, Department of Cardiovascular Sciences, University of Leicester British Heart Foundation Cardiovascular Research Centre and NIHR Leicester Biomedical Research Centre. “In spite of significant advances in treatment in the past 25 years, the prognosis for patients with heart failure remains poor, with risk of premature death and hospital admission.”

“Heart failure can be devastating to those who are affected, impacting on daily activities and leaving people at a greater risk of other vascular complications,” said Dr Juliet Roberts, Medical Director, Boehringer Ingelheim, “The BI/Lilly Alliance is committed to exploring how we can help to support these patients and developing new treatment options for their healthcare professionals.”

Full results from the EMPEROR-Reduced trial will be presented at the European Society of Cardiology (ESC) congress 2020, on 29 August 2020.

The EMPEROR trials are part of the EMPOWER clinical programme, one of 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.¹²

About the EMPEROR Chronic Heart Failure Studies^13,14
The EMPEROR (EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure) chronic heart failure studies are two Phase III, randomised, double-blind trials investigating once-daily empagliflozin compared with placebo in adults with chronic heart failure with preserved or reduced ejection fraction*, both with and without diabetes, who are receiving current standard of care:

·         EMPEROR-Reduced [NCT03057977]: will investigate 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 hospitalisation for heart failure [Time Frame: up to 38 months]
• Anticipated number of patients: 3,730
• Completion: 2020

• EMPEROR-Preserved [NCT03057951]: will investigate 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 hospitalisation for heart failure [Time Frame: up to 38 months]
• Anticipated number of patients: approx. 5,990
• Estimated completion: 2021

*Ejection fraction is a measurement of the percentage of blood the left ventricle pumps out with each contraction. When the heart relaxes, the ventricle refills with blood.
HFrEF occurs when the heart muscle does not contract effectively, and less blood is pumped out to the body compared with a normally functioning heart.

HFpEF occurs when the heart muscle contracts normally but the ventricle does not fill with enough blood, so less blood can enter the heart compared with a normally functioning heart.

About the EMPOWER programme

The Alliance has developed the EMPOWER programme 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.¹⁵ Through the EMPOWER programme, 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 studies, including 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.

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.¹⁶ It is a widespread condition affecting 60 million people worldwide and expected to increase as the population ages.¹⁷ Heart failure is highly prevalent in people with diabetes;¹⁹ however, approximately half of all people with heart failure do not have diabetes^.20

The empagliflozin heart failure programme was initiated based on data from the EMPA-REG OUTCOME^® trial, which assessed the effect of empagliflozin (10 mg or 25 mg once daily) added to standard of care compared with placebo added to standard of care.²¹

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 worldwide and are a leading cause of death.²²

The cardiovascular, renal and metabolic systems are interrelated, 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 interrelated 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, improving the health of one system can lead to positive effects throughout the others.^23,24

Through our research and treatments, we aim to help more people protect the health of their organs, restore balance between the interconnected cardio-renal-metabolic systems and reduce their risk for serious complications. As part of our commitment to those whose health is jeopardised 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. Empagliflozin is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise as monotherapy when metformin is considered inappropriate due to intolerance, in addition to other medicinal products for the treatment of diabetes.

Inhibition of SGLT2 with empagliflozin in people with type 2 diabetes and high blood sugar levels^1,2 prevents sugar being re-absorbed by the kidneys, leading to the excretion of excess sugar in the urine. In addition, initiation of empagliflozin also prevents salt being re-absorbed, leading to increased excretion of salt from the body and reducing the fluid load of the body’s blood vessel system (i.e. intravascular volume).

About Boehringer Ingelheim and Eli Lilly and Company

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance that centres 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.

About Boehringer Ingelheim 
Making new and better medicines for humans and animals is at the heart of what we do. Our mission is to create breakthrough therapies that change lives. Since its founding in 1885, Boehringer Ingelheim has been independent and family-owned. We have the freedom to pursue our long-term vision, looking ahead to identify the health challenges of the future and targeting those areas of need where we can do the most good.

As a world-leading, research-driven pharmaceutical company, more than 51,000 employees create value through innovation daily for our three business areas: Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. In 2019, Boehringer Ingelheim achieved net sales of 19 billion euros. Our significant investment of almost 3.5 billion euros in R&D drives innovation, enabling the next generation of medicines that save lives and improve quality of life.

We realise more scientific opportunities by embracing the power of partnership and diversity of experts across the life-science community. By working together, we accelerate the delivery of the next medical breakthrough that will transform the lives of patients now, and in generations to come.

More information about Boehringer Ingelheim can be found at www.boehringer-ingelheim.co.uk.

About Eli Lilly and Company 
Lilly 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 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 www.lilly.co.uk.