Boehringer Ingelheim and Eli Lilly Announce New Post Hoc Analysis from EMPA-REG OUTCOME® Trial Demonstrating Consistent Cardiorenal Benefits of Empagliflozin in Type 2 Diabetes Patients with Chronic Kidney Disease Regardless of Albuminuria Status

Ingelheim, Germany and Indianapolis, USA, June 12, 2019 /PRNewswire/ -- Boehringer Ingelheim and Eli Lilly and Company announced EMPA-REG OUTCOME^®Novel Post Hoc Analysis Results from Trial Data. These results demonstrated that the effects of empagliflozin on reducing cardiovascular and renal risks were consistent in the subgroup of patients with type 2 diabetes, established cardiovascular disease, and chronic kidney disease without significant albuminuria (elevated urinary protein levels), compared with all other patients in the trial. The findings were presented as an oral report at the 79th Scientific Sessions of the American Diabetes Association (ADA) held in San Francisco, California, USA.

Waheed Jamal, Vice President and Head of Medical Affairs in the Cardiovascular Metabolism Therapeutic Area at Boehringer Ingelheim, stated: “We are pleased to share data from EMPA-REG OUTCOME^®Novel research data from the landmark trial investigating the effects of empagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD)—a population that is becoming increasingly prevalent yet has been understudied. These results confirm the need for further research aimed at addressing the unmet medical needs of patients across the spectrum of kidney disease. To this end, we conducted the large-scale outcomes trial EMPA-KIDNEY, designed to evaluate the impact of empagliflozin on cardiovascular death and progression of kidney disease in a broad population of adults with CKD.”

Globally, more than 500 million people suffer from chronic kidney disease, with up to 40% of these patients having comorbid diabetes.^1,2,3 "Patients with chronic kidney disease often have varying amounts of protein in their urine, which we refer to as proteinuria."⁴However, most patients with chronic kidney disease have normal to moderately increased levels of urinary protein, without significant proteinuria.⁵Renal Diseases Without Significant Proteinuria Are Becoming Increasingly Prevalent, Yet Remain Understudied in Clinical Trials Despite a Marked Increase in the Risk of Adverse Outcomes.⁵

In this novel post hoc analysis of EMPA-REG OUTCOME^®In the subgroup of patients with concurrent chronic kidney disease without significant proteinuria and in all other patients, empagliflozin demonstrated consistent effects in reducing the risk of cardiovascular and renal outcomes. Study endpoints included cardiovascular death, hospitalization for heart failure, new-onset or worsening renal disease, the composite endpoint of cardiovascular death or hospitalization for heart failure, and other relevant safety outcomes.¹

Furthermore, at the recently held 2019 International Society of Nephrology (ISN) World Congress of Nephrology, results from another separate post hoc analysis indicated that, regarding EMPA-REG OUTCOME^®The effects of empagliflozin on cardiac and renal function* were consistent in the subgroup of patients with concurrent proteinuric kidney disease and in all other patients. Collectively, these post hoc analysis results indicate that the impact of empagliflozin on cardiorenal outcomes is consistent, regardless of whether patients have proteinuric kidney disease.

Dr. Sherry Martin, Vice President of Medical Affairs at Eli Lilly and Company, stated, “These new findings are only part of our extensive and comprehensive clinical development program, which aims to investigate how empagliflozin improves patient health outcomes and addresses treatment gaps, positioning it as a broad therapeutic option for cardiometabolic diseases. We look forward to gathering further insights from the EMPA-KIDNEY trial. EMPA-KIDNEY will evaluate the potential of empagliflozin to improve outcomes in patients with chronic kidney disease, including those with and without proteinuria.”

The EMPA-KIDNEY trial will enroll approximately 5,000 adult patients with chronic kidney disease worldwide, regardless of whether they have comorbid diabetes or proteinuria.⁵

*Defined as end-stage renal disease (initiation of maintenance renal replacement therapy or continuouseGFR <15 ml/min/1.73Square Meter), sustained doubling of creatinine, or renal/Cardiovascular Death。

AboutEMPA-KIDNEY: Study on the Cardiorenal Protective Effects of Empagliflozin⁶

EMPA-KIDNEY (NCT03594110) is a multinational, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effect of empagliflozin on clinically relevant outcomes, namely progression of kidney disease and risk of cardiovascular death. The primary outcome was defined as the time to the first occurrence of cardiovascular death or progression of kidney disease, end-stage kidney disease (requiring kidney replacement therapy, such as dialysis or kidney transplantation), or a sustained decline in eGFR to <10 mL/min/1.73 m².Square Meter, kidney death or a sustained decline in eGFR of ≥40% after randomization. EMPA-KIDNEY included patients with confirmed chronic kidney disease, both with and without diabetes, who received either 10 mg empagliflozin or placebo in addition to current standard therapy.

EMPA-KIDNEY is an academic collaborative project independently conducted, analyzed, and reported by the Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford. This unit is affiliated with the Clinical Trial Service Unit (CTSU) and the Epidemiological Studies Unit. Boehringer Ingelheim is funding this research project, committed to further advancing therapeutic and pioneering research to address public health challenges in the fields of cardiovascular, metabolic, and kidney diseases beyond type 2 diabetes.

About Chronic Kidney Disease

Chronic kidney disease is defined as a gradual decline in renal function over time. Approximately two-thirds of chronic kidney disease cases are attributable to metabolic disorders, such as diabetes (known as diabetic nephropathy), obesity, and hypertension.^6,7,8

Notably, chronic kidney disease is associated with increased morbidity and mortality. In patients with chronic kidney disease, most deaths are caused by cardiovascular complications, which typically occur before the onset of end-stage renal disease.^9,10,11Once end-stage renal disease is reached, affected patients must undergo renal replacement therapy, such as chronic dialysis or kidney transplantation.¹²Chronic kidney disease is highly prevalent worldwide, affecting more than 10% of the population.¹³As no drugs have currently been approved specifically to delay the progression of kidney disease and reduce cardiovascular mortality, patients with chronic kidney disease strongly desire novel therapeutic options to address unmet medical needs.

About Empagliflozin

Empagliflozin is an oral, once-daily, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medication with data demonstrating a reduced risk of cardiovascular death included in its labeling in multiple countries.^14,15,16

In patients with type 2 diabetes and hyperglycemia, empagliflozin promotes the urinary excretion of excess glucose by inhibiting SGLT2. Furthermore, empagliflozin use facilitates increased sodium excretion and reduces fluid load on the vascular system (i.e., intravascular volume). In the EMPA-REG OUTCOME^®In the trial, we observed that empagliflozin may help reduce cardiovascular mortality by inducing changes in glucose, sodium, and water metabolism in patients.

Boehringer Ingelheim and Eli Lilly and Company

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced a collaborative agreement in the field of diabetes treatment, covering multiple products across several classes of glucose-lowering medications. This partnership leverages the strengths of two global leading pharmaceutical companies. Through this collaboration, both companies are committed to helping patients with diabetes and focusing on their clinical needs. Depending on the market, the parties will choose to jointly promote or individually promote the respective drugs contributed to this partnership.

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14.Jardiance^® (empagliflozin) tablets U.S. Prescribing Information. Available at: https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed May 2019.
15.European Summary of Product Characteristics Jardiance^®, approved May 2018. Data on file.
16.Jardiance^® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.