Empagliflozin meets primary endpoint in reducing risk of cardiovascular death or hospitalization for heart failure in Phase III trial in adults with and without diabetes

INGELHEIM, Germany & INDIANAPOLIS, US–(BUSINESS WIRE)–Positive top-line results from the EMPEROR-Reduced Phase III trial in adults with heart failure with reduced ejection fraction, with and without diabetes, were announced today by Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY). EMPEROR-Reduced met its primary endpoint, demonstrating superiority with empagliflozin (10 mg) compared to placebo in reducing the risk for the composite of cardiovascular death or hospitalization due to heart failure, when added to standard of care. 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 a new standard of care for this disease, which will be a meaningful addition to currently established treatments.”

Heart failure is the leading cause of hospitalization in the US and Europe, and the number of patients across Asia is also increasing.² The risk of death in people with heart failure rises with each hospital admission.³ 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.⁴ Symptoms associated with heart failure, such as breathlessness and fatigue, can impact quality of life.⁵

“One in five people can expect to develop heart failure in their lifetime, so it is very encouraging to see these positive results from the EMPEROR-Reduced trial demonstrating that empagliflozin improves heart failure outcomes,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “We are excited to share the full results and are working tirelessly to explore how empagliflozin can improve the lives of people living with heart failure.”

Full results from the EMPEROR-Reduced trial will be presented in a hot line session at the European Society of Cardiology (ESC) congress 2020 on 29 August, and regulatory submissions are planned in 2020. A second trial, EMPEROR-Preserved, is exploring the effect of empagliflozin on cardiovascular death or hospitalization in adults with heart failure with preserved ejection fraction – an area with no approved treatment options.^6,7 EMPEROR‑Preserved results are expected in 2021.

The EMPEROR trials are part of the EMPOWER clinical program, 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.

“These results build upon the already established cardiovascular benefits of empagliflozin in adults living with type 2 diabetes and cardiovascular disease,” said Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. “Metabolic conditions that affect the heart and kidneys can lead to serious consequences, including hospitalizations and death. Through our EMPOWER clinical program, we are committed to advancing knowledge about these devastating clinical outcomes. We look forward to seeing how empagliflozin can help adults around the world living with these conditions.”

About the EMPEROR Heart Failure Studies^6,8
The EMPEROR (EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure) chronic heart failure studies are two Phase III, randomized, 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] 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
• Completion: 2020

• EMPEROR-Preserved [NCT03057951] investigates 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 [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 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 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. With more than 27,000 adults enrolled worldwide in clinical trials, 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 It is a widespread condition affecting 60 million people worldwide and expected to increase as the population ages.¹¹ Heart failure is highly prevalent in people with diabetes;¹² however, approximately half of all people with heart failure do not have diabetes.^11,13

The empagliflozin heart failure program 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.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.⁹

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, improving the health of one system can lead to positive effects throughout the others.^15,16

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.^17,18,19

Inhibition of SGLT2 with empagliflozin in people with type 2 diabetes and high blood sugar levels 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). Empagliflozin induces changes to the sugar, salt and water metabolism in the body that may contribute to the reductions in cardiovascular death observed in the EMPA-REG OUTCOME^® trial.²⁰

Please click on the following link for ‘Notes to Editors’ and ‘References’ https://www.boehringer-ingelheim.com/press-release/emperor-reduced-heart-failure-toplineresults