Ingelheim, Germany, and Indianapolis, US, 13 December 2019 – Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced today results from the EMPERIAL-Reduced and EMPERIAL-Preserved studies related to functional endpoints with empagliflozin in adults with chronic heart failure with reduced and preserved ejection fraction, respectively. In both studies, there was no significant change from baseline to week 12 in exercise ability with empagliflozin versus placebo, as measured by the six-minute walk test, which was the primary endpoint of the studies. The safety profile seen in the EMPERIAL studies, which included people with and without diabetes, was similar to the currently known safety profile of empagliflozin, and no new safety risks were identified.
The EMPERIAL studies deliver new safety data for empagliflozin in adults with heart failure who do not have diabetes. In addition, EMPERIAL-Preserved is the first study to deliver safety data for empagliflozin in heart failure with preserved ejection fraction.
“Heart failure affects millions of people worldwide and yet there are currently limited treatment options available for those who live with this challenging condition,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “We are committed to learning more about how empagliflozin could help people living with heart failure through the wider heart failure programme, including the EMPEROR studies. These studies are exploring whether empagliflozin reduces the risk of cardiovascular death and hospitalisation for people with chronic heart failure.”
The EMPERIAL studies used the six-minute walk test, which measures the distance a person can walk in six minutes, to evaluate changes in exercise ability over 12 weeks.1,2 For other heart failure guideline-recommended therapies, there have been divergent results between studies examining clinical outcomes and symptom improvement, with some showing improvements in outcomes such as mortality, but neutral or inconsistent results in exercise ability and patient-reported outcomes.3
The ongoing empagliflozin heart failure programme also includes the EMPEROR-Preserved, EMPEROR-Reduced, EMPULSE and EMPA-VISION studies. The programme, which will include more than 10,000 adults, investigates the effects of empagliflozin on heart failure-related outcomes and patient-related outcomes in people with heart failure.1,2, 4,5,6,7 The EMPERIAL studies were initiated based on data obtained from the EMPA-REG OUTCOME® trial, in which empagliflozin showed a 38 percent relative risk reduction in cardiovascular death and a 35 percent relative risk reduction in hospitalisation for heart failure in adults with type 2 diabetes and established cardiovascular disease, compared to placebo.8
“The EMPERIAL studies highlight our commitment to listening to patients’ needs and studying the impact of our treatments on important measures such as quality of life,” said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Lilly. “Boehringer Ingelheim and Lilly will continue to explore how empagliflozin can potentially improve health outcomes and fill treatment gaps for people with cardiorenal metabolic conditions, including adults with chronic heart failure.”
Full results from the EMPERIAL trials will be shared in 2020.
About EMPERIAL1,2
EMPERIAL consisted of two Phase III randomised, double-blind studies in adults with or without diabetes. The studies evaluated the effect of 12 weeks’ treatment of once-daily empagliflozin 10 mg compared with placebo on exercise ability and heart failure symptoms in patients with chronic heart failure with preserved or reduced ejection fraction.* The primary endpoint was measured by the six-minute walk test, a common measure of exercise ability.
- EMPERIAL-preserved [NCT03448406]: investigated empagliflozin in patients with chronic heart failure with preserved ejection fraction (HFpEF). The study looked at a functional endpoint — how far patients can walk in six minutes — and at heart failure symptoms.
- Primary endpoint: Change from baseline to week 12 in exercise ability as measured by the distance walked in six minutes
- Number of patients enrolled: 315
- Completed: 9 October 2019
- EMPERIAL-reduced [NCT03448419]: investigated empagliflozin in patients with chronic heart failure with reduced ejection fraction (HFrEF). The study looked at a functional endpoint — how far patients can walk in six minutes — and at heart failure symptoms.
- Primary endpoint: Change from baseline to week 12 in exercise ability as measured by the distance walked in six minutes
- Number of patients enrolled: 312
- Completed: 7 October 2019
HFpEF occurs when the heart muscle contracts normally but the ventricle muscles are stiff. They do not relax as they should when the ventricle fills with blood, so less blood can enter the heart compared to a normally functioning heart.
HFrEF occurs when the heart muscle does not contract effectively and less blood is pumped out to the body compared to a normally functioning heart.
Both HFpEF and HFrEF lead to similar symptoms of heart failure, specifically difficulty breathing, swelling and fatigue.
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 It is a widespread condition affecting 60 million people worldwide and expected to increase as the population ages.10 Heart failure is highly prevalent in people with diabetes;11 however, approximately half of all people with heart failure do not have diabetes.12,13
There is a high unmet need in the treatment of heart failure, as approximately 50 percent of people diagnosed with heart failure will die within five years. Additionally, heart failure represents the most common cause of hospitalisation among individuals aged 65 years and over in the US and Europe.12,14
About Cardiorenal Metabolic Conditions
Cardiorenal metabolic conditions are a group of interconnected disorders affecting the heart, kidneys and endocrine system. In aggregate, these conditions are the leading cause of deaths worldwide, accounting for up to 20 million deaths annually.15 Conditions within this group include coronary artery disease, heart failure, chronic kidney disease and type 2 diabetes, among many others.16
Emerging science on the link between the cardiorenal and metabolic systems supports taking a multidisciplinary approach toward diagnostic, preventive and therapeutic strategies for people living with these conditions. A team approach to optimise patient care by coordinating treatment of related comorbidities, including the use of emerging therapies with broad cardiorenal metabolic effects, may improve outcomes for people with serious chronic conditions such as these.
About Empagliflozin
Empagliflozin (marketed as Jardiance®) is an oral, once daily, highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor and the first medicine approved to include cardiovascular death risk reduction data in its type 2 diabetes 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
About 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 to help those living with heart failure or chronic kidney disease.
Currently, no Boehringer Ingelheim and Lilly products are approved for the treatment of heart failure or chronic kidney disease.
Boehringer Ingelheim
Improving the health of humans and animals is the goal of the research-driven pharmaceutical company Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention.
Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas human pharmaceuticals, animal health and biopharmaceuticals. In 2018, Boehringer Ingelheim achieved net sales of around 17.5 billion euros. R&D expenditure of almost 3.2 billion euros, corresponded to 18.1 percent of net sales.
As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment.
About Lilly Diabetes
Lilly has been a global leader in diabetes care since 1923, when we introduced the world's first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research and collaboration, a wide range of therapies and a continued determination to provide real solutions – from medicines to support programmes and more – we strive to make life better for all those affected by diabetes around the world. For more information, visit
www.lillydiabetes.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 chronic kidney disease and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialisation. 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.
CONTACT:
Stefanie Dölz
Product Communication Manager
Boehringer Ingelheim
Phone: +49 (6132) 77 172209
Stephan Thalen
Global Business Communications
Lilly Diabetes
Phone: +1 (317) 276 8304
Footnotes
* Ejection fraction is a measurement expressed as a percentage of the amount of blood that leaves the heart each time it contracts, related to the total blood volume of the heart chambers. During each heartbeat pumping cycle, the heart contracts and relaxes. When the heart contracts, it ejects blood from the two pumping chambers (ventricles). When the heart relaxes, the ventricles refill with blood.
References
1 ClinicalTrials.gov. A phase III randomised, double-blind trial to evaluate the effect of 12 weeks treatment of once daily EMPagliflozin 10 mg compared with placebo on ExeRcise ability and heart failure symptoms, In patients with chronic HeArt FaiLure with reduced Ejection Fraction (HFrEF) (EMPERIAL – reduced). Available at: https://clinicaltrials.gov/ct2/show/NCT03448419?term=EMPERIAL&rank=2. Accessed December 2019.
2 ClinicalTrials.gov. A phase III randomised, double-blind trial to evaluate the effect of 12 weeks treatment of once daily EMPagliflozin 10 mg compared with placebo on ExeRcise ability and heart failure symptoms, In patients with chronic HeArt FaiLure with preserved Ejection Fraction (HFpEF) (EMPERIAL – preserved). Available at: https://clinicaltrials.gov/ct2/show/NCT03448406?term=EMPERIAL&rank=1. Accessed December 2019.
3 US Food and Drug Administration. Treatment for Heart Failure: Endpoints for Drug Development: Guidance for Industry. June 2019. Available at https://www.fda.gov/media/128372/download. Accessed December 2019.
4 Packer M, Butler J, Filippatos GS, et al. Evaluation of the effect of sodium–glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection
fraction: rationale for and design of the EMPEROR-Reduced trial. Eur J Heart Fail. 2019. doi:10.1002/ejhf.1536.
5 Anker SD, Butler J, Gerasimos S, et al. Evaluation of the Effect of SGLT2 Inhibition With Empagliflozin on the Morbidity and Mortality of Patients With Chronic Heart Failure and a Preserved Ejection Fraction: Rationale for and Design of the EMPEROR-Preserved Trial. Eur J Heart Fail. 2019. doi: 10.1002/ejhf.1596.
6 ClinicalTrials.gov. EMPagliflozin initiated in patients hospitalised for acUte heart faiLure (de novo or decompensated chronic HF) who have been StabilisEd (EMPULSE) Available at: https://www.clinicaltrials.gov/ct2/show/NCT04157751. Accessed December 2019.
7 ClinicalTrials.gov. A Study That Looks at the Function of the Heart in Patients With Heart Failure Who Take Empagliflozin (EMPA-VISION). Available at: https://clinicaltrials.gov/ct2/show/NCT03332212. Accessed December 2019.
8 Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373:2117-28.
9 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. The Lancet 2018;392(10159):P1789-1858.
10 American Heart Association. What is Heart Failure? Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure. Accessed December 2019.
11 Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;128(16):e240-e327.
12 Ambrosy AP, Fonarow GC, Butler J, et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63(12)1123-33.
13 Suskin N, McKelvie RS, Burns RJ, et al. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J. 2000;21:1368-75.
14 Ponikowski P, Anker SG, AlHabib KF, et al. Heart failure: Preventing disease and death worldwide. ESC Heart Fail. 2014;1(1):4-25.
15 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. The Lancet. 2016; 388(10053):1459–544.
16 Arnold SV, Kosiborod M, Wang J, et al. Burden of cardio-renal-metabolic conditions in adults with type 2 diabetes within the Diabetes Collaborative Registry. Diabetes, Obesity and Metabolism. 2018;20(8):2000-2003.
17 Jardiance® (empagliflozin) tablets. U.S. Prescribing Information, approved October 2018.
18 Jardiance® (empagliflozin) tablets. European Summary of Product Characteristics, approved February 2019.
19 Jardianz® (empagliflozin) tablets. Mexican Full Prescribing Information, approved August 2017.
20 Vallon V and Thompson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia 2017;60(2):215-25.
