• EMPULSE is a superiority study that will assess the clinical benefit, safety and tolerability of 10 mg daily empagliflozin in acute heart failure1

INGELHEIM, Germany & INDIANAPOLIS, IN, USA I November 12, 2019 I Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) today announced the initiation of EMPULSE, the sixth Phase III study in the empagliflozin heart failure programme. The study will assess whether in-hospital administration of empagliflozin 10 mg daily improves heart failure outcomes when initiated in people hospitalised for any type of acute heart failure event once they have been stabilised. The study will include participants both with and without type 2 diabetes.

Heart failure is the leading cause of hospitalisation in Europe and the US, and half of people with heart failure are expected to die within five years of diagnosis.2,3 However, outcomes for patients after they have been hospitalised for heart failure are poor, with a 15 percent mortality and 30 percent readmission rate within 60 to 90 days of discharge from hospital.4 Initiating treatment in hospital is one of the best predictors of long-term improved prognosis and patient treatment adherence.5 The EMPULSE study aims to understand whether empagliflozin has the potential to improve outcomes in this population.

“Acute decompensated heart failure is one of the fastest-growing diseases in the world and a leading cause of hospital admissions worldwide with high short term mortality and rehospitalisation. Unlike chronic heart failure, there is no established therapy available that improves clinical outcomes in acute heart failure,” said Adriaan Voors, Professor of Cardiology, University Medical Center Groningen, Netherlands. “The beneficial effects of SGLT2 inhibitors, as seen in three large randomised trials in type 2 diabetes patients, are thought to be at least partly explained by the diuretic/natriuretic effects of SGLT2 inhibitors. The EMPULSE study will investigate whether empagliflozin, due to its mode of action, can alleviate symptoms associated with heart failure and improve outcomes after discharge from the hospital.”

The primary outcome of the study will be net clinical benefit, a composite of all-cause mortality, number of heart failure events (including hospitalisations, urgent heart failure visits and unplanned patient visits), time to first heart failure event and change from baseline in Kansas City Cardiomyopathy Questionnaire – Clinical Summary Score (KCCQ-CSS), an instrument for measuring disease-specific quality of life in heart failure.1

“We are particularly delighted to announce the addition of EMPULSE as the first-ever study to assess the effects of empagliflozin in people who have been hospitalised for acute heart failure,” said Mohamed Eid, M.D., M.P.H., M.H.A., Vice President, Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc. “The study aims to address an unmet need and is an important addition to our broad and comprehensive heart failure programme.”

EMPULSE is part of the empagliflozin heart failure programme, which also consists of the EMPEROR-Reduced and EMPEROR-Preserved, EMPERIAL-Preserved and EMPERIAL-Reduced, and EMPA-VISION studies. These studies are investigating the effects of empagliflozin on heart failure-related outcomes and functional capacity in more than 9,500 adults with heart failure, including those with and without diabetes.6,7,8,9,10

About EMPULSE (NCT04157751)
The EMPULSE study is a multicentre, randomised, double-blind, 90-day superiority study to evaluate the effect on clinical benefit, safety and tolerability of once-daily oral EMPagliflozin 10 mg compared to placebo, initiated in patients hospitalised for acUte heart faiLure (de novo or decompensated chronic HF) who have been StabilisEd (EMPULSE).

  • Primary endpoint: Net clinical benefit, a composite of all-cause mortality, number of heart failure events (including hospitalisations for heart failure, urgent heart failure visits and unplanned outpatient visits), time to first heart failure event and change from baseline in Kansas City Cardiomyopathy Questionnaire – Clinical Summary Score (KCCQ-CSS) after 90 days of treatment.
  • Anticipated number of patients: approximately 500.

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.11 It is a widespread condition affecting 60 million people worldwide and expected to increase as the population ages.12 Heart failure is highly prevalent in people with diabetes;13 however, approximately half of all people with heart failure do not have diabetes.2,14

Symptoms of heart failure include difficulty breathing, swelling – most commonly in feet, legs and ankles – and fatigue, among others.15 People with heart failure experience a substantial reduction in quality of life, approximately 76 percent of whom find it difficult to carry out usual activities.16 This is, in part, due to the limitation of physical activity.

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.17 Additionally, heart failure represents the most common cause of hospitalisation among individuals aged 65 years and over in the US and Europe.2

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 the label in several countries. 18,19,20

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.21

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. 

More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: http://annualreport.boehringer-ingelheim.com.

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 (link is external).

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 (link is external) and lilly.com/newsroom (link is external).

References

1 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 November 2019.
2 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.
3 Ponikowski P, Anker SG, AlHabib KF, et al. Heart failure: Preventing disease and death worldwide. ESC Heart Fail. 2014;1(1):4-25.
4 Greene SJ, Fonarow GC, et al. The vulnerable phase after hospitalization for heart failure. Nat Rev Cardiol. 2015;12(4):220-9.
5 Aditi A, Bhagat, et.al. Initiation, Continuation, Switching, and Withdrawal of Heart Failure Medical Therapies During Hospitalisation. JACC:HF. 2019;7(1):1-12.
6 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.
7 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.
8 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 (link is external). Accessed November 2019.
9 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 (link is external). Accessed November 2019
10 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 November 2019.
11 American Heart Association. What is Heart Failure? Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure (link is external). Accessed November 2019.
12 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.
13 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.
14 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.
15 Watson RDS, Gibbs CR, Lip GYH. Clinical features and complications. BMJ. 2000;320(7229):236-39.
16 Calvert MJ, Freemantle N and Cleland JG. The impact of chronic heart failure on health-related quality of life data acquired in the baseline phase of the CARE-HF study. Eur J Heart Fail. 2005;7(2):243-51.
17 Ponikowski P, Anker SG, AlHabib KF, et al. Heart failure: Preventing disease and death worldwide. ESC Heart Fail. 2014;1(1):4-25.
18 Jardiance® (empagliflozin) tablets U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf (link is external). Accessed November 2019.
19 European Summary of Product Characteristics Jardiance®, approved May 2018. Data on file. 
20 Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.
21 Vallon V and Thompson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017;60(2):215-225.

SOURCE: Boehringer Ingelheim