Jardiance® (empagliflozin) reduced the risk for the composite primary endpoint of cardiovascular death or hospitalization for heart failure and slowed kidney function decline in adults with heart failure with left ventricular ejection fraction (LVEF) over 40% regardless of chronic kidney disease status at baseline, according to findings from a new prespecified sub-analysis of the EMPEROR-Preserved® phase III trial. In EMPEROR-Preserved, two thirds of enrolled adults had heart failure with preserved ejection fraction (HFpEF; LVEF of at least 50%) and one third had mildly reduced LVEF (greater than 40% but less than 50%). The results were presented today at the American Society of Nephrology Kidney Week 2021, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.
"Heart failure and chronic kidney disease are intimately linked - the risk of death in people with heart failure increases with kidney function decline," said Faiez Zannad, M.D., Ph.D., EMPEROR Program clinical investigator and Emeritus Professor of Therapeutics and Cardiology at the University of Lorraine, France. "The consistent benefits shown for the reduction of serious heart failure events and the slowing of kidney function decline regardless of chronic kidney disease status are welcome results for both patients and physicians. The findings underscore the potential value of empagliflozin across a wide range of kidney function in this heart failure population that includes people with preserved ejection fraction."
Nearly half of adults with heart failure also have chronic kidney disease. Together, these conditions are associated with high mortality rates and risk for hospital admission. More than 6 million people in the U.S. have heart failure, and approximately half of them have HFpEF. No currently approved treatments have been clinically proven to significantly improve outcomes across the full spectrum of heart failure.
"Heart failure, especially with preserved ejection fraction, is a complex, difficult-to-treat condition, and the prognosis only worsens with the combined burden of chronic kidney disease," 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 encouraging results from this sub-analysis further demonstrate the potential for Jardiance to offer a treatment option for adults with cardio-renal-metabolic conditions."
As previously reported, EMPEROR-Preserved showed that Jardiance significantly reduced the risk for the composite primary endpoint of cardiovascular death or hospitalization for heart failure in adults with heart failure with LVEF over 40% compared with placebo. Jardiance also significantly reduced the risk of first and recurrent hospitalizations for heart failure and slowed kidney function decline.
Over half (53.5%) of adults in EMPEROR-Preserved had chronic kidney disease (defined as eGFR below 60 mL/min/1.73 m2 or UACR above 300 mg/g) at trial entry, and 9.7% had severe kidney impairment (eGFR below 30 mL/min/1.73 m2). The new prespecified sub-analysis of EMPEROR-Preserved demonstrated that the benefits seen in the overall population were consistent in adults with and without chronic kidney disease. Jardiance consistently improved cardiovascular outcomes and slowed kidney function decline across the full range of kidney function down to an eGFR of 20 mL/min/1.73 m2. Jardiance was well tolerated regardless of the level of baseline kidney function.
"This data marks an important milestone for the growing number of people living with both heart failure and chronic kidney disease, many of whom are in need of additional treatment options for these interconnected, complex conditions," said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Lilly. "We look forward to continuing research with the goal of addressing the unmet needs of those with kidney impairment, including through our EMPA-KIDNEY phase III trial of Jardiance, from which we eagerly await a readout next year."
The U.S. Food and Drug Administration (FDA) previously granted Fast Track designation for the development of Jardiance to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with chronic heart failure (New York Heart Association [NYHA] Class II-IV). The Fast Track designation is for the EMPEROR program, which consists of the EMPEROR-Reduced® and EMPEROR-Preserved trials. The EMPEROR-Reduced results formed the basis of the recent FDA approval for heart failure with reduced ejection fraction. Based on results from EMPEROR-Preserved, the FDA granted Breakthrough Therapy designation for Jardiance as an investigational treatment for adults with HFpEF. Jardiance is not indicated for the treatment of HFpEF.
In March 2020, the FDA also granted Fast Track designation to Jardiance for the treatment of chronic kidney disease. This designation covers the ongoing EMPA-KIDNEY trial, which is investigating the effect of Jardiance on the progression of kidney disease and occurrence of cardiovascular death in adults with established chronic kidney disease, with and without diabetes. Jardiance is not indicated for the treatment of chronic kidney disease.
