CHMP issues positive opinion to expand Jardiance (empagliflozin) indication based on unprecedented benefit in adult heart failure patients with preserved ejection fraction

Ingelheim, Germany, 28.01.2022 – The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted a positive opinion recommending Jardiance® (empagliflozin) for the treatment of adults with symptomatic chronic heart failure, Boehringer Ingelheim and Eli Lilly and Company announced today.¹ Empagliflozin was previously approved for the treatment of adults with symptomatic chronic heart failure with reduced ejection fraction (HFrEF).⁴ If approved, the positive opinion would expand this indication to be applicable for adults across the full spectrum of left ventricular ejection fraction (LVEF), including preserved ejection fraction (HFpEF).

“For the very first time, we now have a treatment that will improve clinical results across the full spectrum of heart failure patients – regardless of ejection fraction,” said Professor Stefan Anker, Heart Failure Cardiologist at Charité Berlin, Germany, and EMPEROR-Preserved Principal Investigator. “Half of all heart failure patients are those with a preserved left ventricular ejection fraction. They suffer symptomatically and have poor outcomes due to the absence of any approved beneficial therapies. Today’s positive opinion of EMA is a significant step forward in redefining clinical practice and will provide an additional lifeline to the millions of patients in Europe diagnosed with HFpEF.”
 
The positive opinion 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 added to standard of care, in 5,988 adults with heart failure with LVEF over 40%.⁵ In the trial, empagliflozin demonstrated an impressive 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. The benefit was regardless of ejection fraction or diabetes status.⁵

“We are delighted with the CHMP’s decision to recommend empagliflozin as a treatment for adults with chronic heart failure,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “Understanding of the interconnected cardio, renal and metabolic systems enabled us to broaden from diabetes to heart failure, following the science to provide solutions to medicine’s greatest challenge. We are proud to provide renewed hope to underserved patients, underscored by the unprecedented clinical benefit seen in the EMPEROR-Preserved clinical trial.”

“Today’s positive opinion addresses the single largest unmet need in cardiovascular medicine, confirming the potential of empagliflozin across the full spectrum of ejection fraction. We are committed to ongoing research in these underserved areas, and look forward to the results from the EMPA-KIDNEY trial, exploring the potential of empagliflozin in chronic kidney disease,” continued Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. 

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^6,7
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.⁸ 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 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.^9,10 It is a widespread condition affecting over 60 million people worldwide and expected to increase as the population ages.^3,11 Heart failure is highly prevalent in people with diabetes; however, approximately half of all people with heart failure do not have diabetes.^12,13

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.^11,14

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.^14,15,16

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 

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 clinical trials to evaluate empagliflozin as a treatment for adults with heart failure and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that empagliflozin will receive additional regulatory approvals. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. 

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: +1 (317) 903-5640
 

References

¹ Committee for Medicinal Products for Human Use (CHMP). Jardiance summary of opinion. Available at: https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-jardiance-ii-0060_en.pdf Accessed: January 2022.
² Andersen MJ, Borlaug BA. Heart failure with preserved ejection fraction: current understandings and challenges. Curr Cardiol Rep. 2014 Jul;16(7):501.
³ Lippi G, Sanchis-Gomar F. Global epidemiology and future trends of heart failure. AMJ. 2020;5:15
⁴ Committee for Medicinal Products for Human Use (CHMP). Jardiance European Public Assessment Report (EPAR) summary. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/jardiance. Accessed: January 2022.
⁵ 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.
⁶ ClinicalTrials.gov. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced). Available at: https://clinicaltrials.gov/ct2/show/NCT03057977. Accessed: January 2022.
⁷ 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. Accessed: January 2022.
⁸ GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388(10053):1459–544.
⁹ American Heart Association. What is Heart Failure? Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure. Accessed: January 2022.
¹⁰ American Heart Association. Types of Heart Failure. Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/types-of-heart-failure. Accessed: January 2022.
¹¹ GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.
¹² Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121–41.
¹³ 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.
¹⁴ Thomas M, Cooper M, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2015;12:73–81.
¹⁵ García-Donaire JA, Ruilope LM. Cardiovascular and Renal Links along the Cardiorenal Continuum. Int J Nephrol. 2011;2011:975782.
¹⁶ Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246–58.
¹⁷ Jardiance® (empagliflozin) tablets. European Product Information, approved April 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_en.pdf. Accessed: January 2022.
¹⁸ Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed: January 2022.