Boehringer Ingelheim: Jardiance® reduced the risk of cardiovascular death

CHMP adopts a positive opinion acknowledging that Jardiance® reduces the risk of CV death

In the EMPA-REG OUTCOME® trial Jardiance® reduced the risk of cardiovascular (CV) death by 38 percent vs placebo in patients with type 2 diabetes (T2D) and established CV disease when added to standard of care1
The Committee for Medicinal Products for Human Use (CHMP) recommends to update the existing label of Jardiance® (empagliflozin) for the treatment of adults with insufficiently controlled type 2 diabetes2
This is the first time the CHMP supports the use of a diabetes treatment for its effect on both glycemic control and cardiovascular events

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion to update the Jardiance® (empagliflozin) label including a change to the indication statement.1 The CHMP recommends Jardiance® for the treatment of adults with insufficiently controlled type 2 diabetes mellitus (T2D) as an adjunct to diet and exercise. The recommended product information now includes data on the reduction of risk of cardiovascular (CV) death in patients with T2D and established CV disease in addition to data on the improvement of blood sugar control in patients with T2D.1 Jardiance® is the only oral diabetes treatment shown to reduce the risk of CV death in a dedicated CV outcome trial to date.2

The positive opinion is based on results from the EMPA-REG OUTCOME® trial. The trial demonstrated that Jardiance® significantly reduced the risk of the primary endpoint of cardiovascular death, non-fatal heart attack or non-fatal stroke by 14 percent versus placebo when added to standard of care in adults with T2D and established CV disease. Taking Jardiance® on top of standard of care reduced the risk of dying from cardiovascular disease by 38 percent.2 There were no statistically significant differences in the risk of non-fatal heart attack or non-fatal stroke.

“Cardiovascular disease is the number one cause of death among people with type 2 diabetes. The life expectancy of people with type 2 diabetes and cardiovascular disease is up to 12 years shorter. There is a significant need for therapies which add to and go beyond the current standard of care,” said Professor Hans-Juergen Woerle, Global Vice President Medicine, Therapeutic Area Metabolism, Boehringer Ingelheim. “Therefore, this recommendation by the CHMP is an important step towards addressing and reducing the burden of cardiovascular mortality for people with type 2 diabetes.”

On December 2, the U.S. Food and Drug Administration (FDA) approved a new indication for Jardiance® to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

About the EMPA-REG OUTCOME® Trial

EMPA-REG OUTCOME® was a long-term, multicentre, randomised, double-blind, placebo-controlled trial of more than 7,000 patients from 42 countries with T2D and established CV disease.2

The study assessed the effect of Jardiance® (10 mg or 25 mg once daily) added to standard of care compared with placebo added to standard of care. Standard of care was comprised of sugar-lowering agents and CV drugs (including for blood pressure and cholesterol). The primary endpoint was defined as time to first occurrence of CV death, non-fatal heart attack or non-fatal stroke.2

Over a median of 3.1 years, Jardiance® significantly reduced the risk of CV death, non-fatal heart attack or non-fatal stroke by 14 percent versus placebo. The risk of CV death was reduced by 38 percent, with no significant difference in the risk of non-fatal heart attack or non-fatal stroke.2

The overall safety profile of Jardiance® in the EMPA-REG OUTCOME® trial was consistent with that of previous trials.2

About Diabetes and Cardiovascular Disease

More than 415 million people worldwide have diabetes, of which 193 million are estimated to be undiagnosed.3 By 2040, the number of people with diabetes is expected to rise to 642 million people worldwide.3 T2D is the most common form of diabetes, responsible for up to 91 percent of diabetes cases in high-income countries.3 Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.3

Due to the complications associated with diabetes, such as high blood sugar, high blood pressure and obesity, CV disease is a major complication and the leading cause of death associated with diabetes.4,5 People with diabetes are two to four times more likely to develop CV disease than people without diabetes.4 In 2015, diabetes caused 5 million deaths worldwide, with CV disease as the leading cause.3,4 Approximately 50 percent of deaths in people with T2D worldwide are caused by CV disease.6,7

About Jardiance®

Jardiance® (empagliflozin) is an oral, once daily, highly selective sodium-glucose co-transporter-2 (SGLT2) inhibitor approved for use in Europe, the United States and other markets around the world for the treatment of adults with type 2 diabetes.

Inhibition of SGLT2 with Jardiance® (empagliflozin) in patients with T2D and high blood sugar levels leads to excretion of excess sugar in the urine. In addition, initiation of Jardiance® increases excretion of salt from the body (i.e. sodium) and reduces the fluid load of the body’s blood vessel system (i.e. intravascular volume). Excretion of sugar, salt and water after the initiation of treatment with empagliflozin may therefore contribute to the improvement in cardiovascular outcomes.

The change to the existing indication adopted by the CHMP is as follows:1

Jardiance is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise

as monotherapy when metformin is considered inappropriate due to intolerance
in addition to other medicinal products for the treatment of diabetes

For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1.

Jardiance® is not approved for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine).

Boehringer Ingelheim and Eli Lilly and Company

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centres on compounds representing several of the largest diabetes treatment classes. This alliance leverages the strengths of two of the world’s leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com (link is external).

Boehringer Ingelheim

Boehringer Ingelheim is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally through 145 affiliates and a total of some 47,500 employees. The focus of the family-owned company, founded in 1885, is on researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects through, for example, the initiative ‘Making More Health’, while also caring for employees. Respect, equal opportunity and reconciling career and family form the foundation of mutual cooperation. The company also focuses on environmental protection and sustainability in everything it does.

In 2015, Boehringer Ingelheim achieved net sales of about 14.8 billion euros. R&D expenditure corresponds to 20.3 percent of net sales.

For more information please visit www.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 programs 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 healthcare leader that unites caring with discovery to 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 www.lilly.com (link is external) and newsroom.lilly.com/social-channels (link is external).

References

1. Zinman B, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015;373:2117–28.

2. CHMP Meeting Highlights, published on December 16, 2016. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/002677/WC500218154.pdf

3. International Diabetes Federation. IDF Diabetes Atlas, 7th edition. Brussels, Belgium 2015. Available at: www.diabetesatlas.org/ Last accessed November 2016.

4. World Heart Federation. Diabetes as a risk factor for cardiovascular disease. Available at: www.world-heart-federation.org/cardiovascular-health/cardiovascular-disease-risk-factors/diabetes. Last accessed November 2016.

5. World Health Organisation. Diabetes: fact sheet no. 312. Available at: www.who.int/mediacentre/factsheets/fs312/en/#. Last accessed November 2016.

6. Nwaneri C, et al. Mortality in type 2 diabetes mellitus: magnitude of the evidence from a systematic review and meta-analysis. The British Journal of Diabetes & Vascular Disease 2013;13:192–207.

7. Morrish NJ, et al. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 2001;44(2):S14–21.