US FDA approves Jardiance® (empagliflozin) to treat adults with heart failure regardless of left ventricular ejection fraction

Ingelheim, Germany and Indianapolis, U.S., 25 February 2022 – The U.S. Food and Drug Administration (FDA) has approved empagliflozin 10 mg to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced today.

Empagliflozin is not for people with type 1 diabetes as it may increase the risk of diabetic ketoacidosis in these patients. It is not for use to improve glycemic control in adults with type 2 diabetes with an eGFR below 30 mL/min/1.73 m⁵ as it is likely to be ineffective in this setting based upon its mechanism of action.

Empagliflozin can be initiated in adults with heart failure with an eGFR as low as 20 mL/min/1.73 m^2.5

“In its phase III trials, empagliflozin has shown a statistically significant and clinically meaningful benefit in patients with heart failure across the spectrum of ejection fraction,” said Javed Butler, M.D., chairman, Department of Medicine, University of Mississippi. “Today’s approval means these demonstrated benefits can now help to address a significant unmet need for the approximately 3 million adults in the U.S. with preserved ejection fraction, a form of heart failure that has very limited treatment options.”

Affecting more than 6 million people in the U.S., heart failure is a leading cause of hospitalization and is becoming increasingly prevalent due to the aging population.^3,6 Just six months ago, Jardiance was approved to reduce the risk of cardiovascular death plus hospitalization for one type of heart failure – heart failure with reduced left ventricular ejection fraction (LVEF). Today’s decision expands this indication to include all adults with heart failure. As a result, the indication now includes adults with preserved LVEF. 

Empagliflozin is contraindicated in people with hypersensitivity to empagliflozin or any of the excipients in Jardiance, as reactions such as angioedema have occurred, and in patients on dialysis. 

This approval is based on results from the landmark EMPEROR-Preserved® phase III trial, which investigated the effect of empagliflozin 10 mg compared with placebo once daily, both on top of standard of care therapy, in 5,988 adults with heart failure with LVEF over 40%. In the trial, Jardiance 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.⁷ In both EMPEROR-Preserved and EMPEROR-Reduced, the benefit was generally consistent across LVEF subgroups.^7,8

A key secondary endpoint analysis from EMPEROR-Preserved showed that Jardiance reduced the relative risk of first and recurrent hospitalizations for heart failure by 27% (407 events for Jardiance vs. 541 for placebo, 0.73 HR, 0.61-0.88 95% CI).⁸

“The FDA approval is very welcome news for people living with heart failure in the U.S. 
We now look forward to further approvals globally to bring empagliflozin treatment to many more heart failure patients, across the range of their left ventricular ejection fraction,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “The significant clinical benefits seen in the EMPEROR-Preserved clinical trial gives clinicians an opportunity to redefine the way we approach the treatment of heart failure and is a significant step forward in this area of unmet need for patients.”

“This approval reinforces the potential of Jardiance as a crucial treatment option to help fill an urgent need for adults across the full spectrum of heart failure,” said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Lilly. “Building on the indication for heart failure with reduced ejection fraction last year, this decision marks the third U.S. FDA approval for empagliflozin stemming from the EMPOWER program and adds to a growing legacy of leadership for the Boehringer Ingelheim and Lilly Alliance spanning cardiovascular disease and type 2 diabetes.”

About the EMPEROR heart failure clinical trials^9,10
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.
  • 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

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.¹¹ 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.^12,13 It is a widespread condition affecting over 15 million people in Europe¹⁴ and over 60 million people worldwide and expected to increase as the population ages.^4,15 Heart failure is highly prevalent in people with diabetes; however, approximately half of all people with heart failure do not have diabetes.¹⁶

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.^17,18,19

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.^5,20

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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⁷ Anker S, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;10.1056/NEJMoa2107038. 
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