Jardiance Demonstrates Consistent Cardio-Renal Benefits in Heart Failure Patients Regardless of Baseline Kidney Function

Nov. 07, 2021 /BioonBIOON/ --Boehringer Ingelheim andEli Lilly(Eli Lilly) recently announced the results of a new pre-specified subgroup analysis from the landmark Phase 3 EMPEROR-Preserved trial (NCT03057951) at the 2021 American Society of Nephrology Kidney Week (ASN Kidney Week). The data showed that,In adult patients with heart failure (HF) and a left ventricular ejection fraction (LVEF) >40%, regardless of baseline chronic kidney disease (CKD) status, treatment with the SGLT2 inhibitor Jardiance (Chinese brand name: Outangjing, generic name: empagliflozin) reduced the risk of the composite primary endpoint of cardiovascular death or hospitalization for heart failure and slowed the decline in renal function.

In this study, two-thirds of the enrolled patients had heart failure with preserved ejection fraction (HFpEF, LVEF ≥ 50%), and one-third had mildly reduced LVEF (40% < LVEF < 50%).HF and CKD are closely linked, with CKD present in nearly half of adult HF patients.. The risk of mortality in patients with heart failure (HF) increases as renal function declines. Regardless of chronic kidney disease (CKD) status, Jardiance demonstrated consistent benefits in reducing serious heart failure events and slowing the decline in renal function, highlighting its potential value across a broad HF population with varying renal function, including patients with heart failure with preserved ejection fraction (HFpEF).

Previously published results showed that in adult patients with HF and LVEF > 40%, Jardiance significantly reduced the risk of the composite primary endpoint of cardiovascular death or heart failure hospitalization compared with placebo. Additionally, Jardiance significantly reduced the risk of first and subsequent heart failure hospitalizations and slowed the decline in renal function.

At baseline, more than half (53.5%) of adult patients had CKD (defined as eGFR <60 mL/min/1.73 m² or UACR >300 mg/g), and 9.7% had severe renal impairment (eGFR <30 mL/min/1.73 m²). A new prespecified subgroup analysis showed that,The treatment benefits of Jardiance observed in the overall population are consistent with those observed in adult patients with and without CKD.。Across the entire range of renal function (eGFR down to 20 mL/min/1.73 m²), Jardiance consistently improves cardiovascular outcomes and slows the decline in renal function.. Regardless of baseline renal function, Jardiance was well tolerated.

Mohamed Eid, Vice President, Clinical Development and Medical Affairs, Cardiometabolic and Respiratory Medicine at Boehringer Ingelheim, stated: “Heart failure, particularly heart failure with preserved ejection fraction (HFpEF), is a complex and difficult-to-treat condition, and its prognosis only worsens with the cumulative burden of chronic kidney disease. The encouraging results from this subanalysis further underscore the potential of Jardiance to provide a treatment option for adults with cardiorenal-metabolic diseases.”

Eli LillyJeff Emmick, Vice President of Product Development, said: "For the growing number of patients with heart failure and chronic kidney disease, these data represent a significant milestone, as many of these patients require additional treatment options for these interrelated and complex conditions. We look forward to continuing our research to address unmet medical needs in patients with impaired kidney function, including through our EMPA-RENDY Phase 3 trial of Jardiance, and we eagerly anticipate the results next year."

EMPEROR-Preserved Primary Endpoints and Heart Failure Hospitalization Outcomes (Click image to view full size)

Previously, the FDA granted Fast Track Designation (FTD) to the EMPEROR development program for Jardiance to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure (NYHA Class II-IV). The EMPEROR program includes the EMPEROR-Reduced trial and the EMPEROR-Preserved trial. The results of the EMPEROR-Reduced trial formed the basis for the recent FDA approval of Jardiance for the treatment of heart failure with reduced ejection fraction (HFrEF). Based on the results of the EMPEROR-Preserved trial,FDAJardiance was also granted Breakthrough Therapy Designation (BTD) for the treatment of adult patients with HFpEF. Currently, Jardiance is not indicated for the treatment of HFpEF.

March 2020,FDAThe FTD for Jardiance in the treatment of CKD was also granted. This designation covers the ongoing EMPA-RENDY trial, which is investigating Jardiance in patients with or withoutDiabetes Mellituseffect on the progression of kidney disease and the incidence of cardiovascular death in adult patients with CKD. Currently, Jardiance is not indicated for the treatment of CKD.

The landmark Phase 3 EMPEROR-Preserved trial evaluated the efficacy and safety of Jardiance in adult patients with HFpEF. The trial enrolled a total of 5,988 patients with heart failure, of whom 4,005 had a left ventricular ejection fraction (LVEF) ≥50% and 1,983 had an LVEF <50%. In the trial, patients were randomized to receive either oral Jardiance 10 mg once daily (n=2,997) or placebo (n=2,991), in addition to guideline-directed heart failure therapy.

The results showed that the trial met the composite primary endpoint:In adult patients with HFpEF, compared with placebo, Jardiance reduced the relative risk of cardiovascular death or hospitalization for heart failure by 21%, demonstrating impressive efficacy. This benefit was independent of ejection fraction or# Diabetes mellitusState-independent. Key secondary endpoint analysis showed:Compared with placebo, Jardiance also reduced the relative risk of first and recurrent hospitalizations for heart failure by 27% and significantly delayed the decline in renal function.. In this trial, the safety profile of Jardiance was generally consistent with its known safety profile. The complete data have been published in *The New England Journal of Medicine* (NEJM) under the title:Empagliflozin in Heart Failure with a Preserved Ejection Fraction。

Data from the EMPEROR-Preserved trial complemented the results of the earlier phase 3 EMPEROR-Reduced trial; the latter trial showed: (1)In adult patients with heart failure with reduced ejection fraction (HFrEF), when added to standard of care, Jardiance 10 mg significantly reduced the composite relative risk of cardiovascular death or hospitalization for heart failure by 25% compared with placebo, and this result was consistent in patients with and without type 2Diabeteswas consistent in the patient subgroup with (T2D)。(2) Analysis of key secondary endpoints showed that,Compared with placebo, Jardiance reduced the relative risk of first and recurrent hospitalizations for heart failure by 30% and significantly slowed the decline in renal function.

In conclusion,These studies demonstrated the benefits of Jardiance® in patients across the entire heart failure disease spectrum, including HFrEF and HFpEF.. inEli LillyIn the released third-quarter financial report, the company disclosed that, in partnership with Boehringer Ingelheim, it has submitted an application to U.S. and EU regulatory authorities for Jardiance for the treatment of HFpEF. If approved, Jardiance will become the first treatment clinically validated across the entire heart failure spectrum,Will Provide Patients with Heart Failure an Opportunity to Fundamentally Transform Their Future. In the United States, more than 6 million people have heart failure, approximately half of whom have HFpEF, also known as diastolic heart failure. Currently, there are no approved therapies that can significantly improve outcomes across the full spectrum of HF. Given its prevalence, adverse outcomes, and the lack of clinically proven treatments to date, HFpEF has been described as the greatest unmet need in cardiovascular medicine.

Heart failure (HF) affects over 60 million people worldwide, and there remains a significant unmet medical need in its treatment, as approximately half of those diagnosed are expected to die within five years. HF is the leading cause of hospitalization among adults aged 65 and older. HF is the most common and severe complication following a heart attack, occurring when the heart cannot pump sufficient blood to the rest of the body. Patients with HF frequently experience shortness of breath and fatigue, which can severely impair quality of life.

Patients with HF often also have impaired renal function, which can significantly and adversely affect prognosis. The mortality risk in HF patients increases with each hospitalization. Heart failure with reduced ejection fraction (HFrEF) occurs when the heart muscle cannot contract effectively, resulting in less blood being pumped from the heart into the body compared to a normally functioning heart. Heart failure with preserved ejection fraction (HFpEF) occurs when the heart muscle contracts normally but there is insufficient blood in the ventricles, meaning less blood enters the heart compared to a normally functioning heart.

Jardiance (Outangjing, empagliflozin) is an oral, once-daily, highly selective SGLT2 inhibitor. The emerging class of SGLT2 inhibitors has been demonstrated to inhibit renal glucose reabsorption, facilitating the excretion of excess glucose from the body and thereby lowering blood glucose levels. Furthermore, this glucose-lowering effect is independent of β-cell function and insulin resistance. Beyond its well-established glycemic efficacy, the drug also confers additional clinical benefits, including weight reduction, blood pressure lowering, and decreased uric acid levels. Jardiance exhibits a favorable safety profile and can reduce# DiabetesReduces the risk of cardiovascular events in patients and is the world's first type 2 diabetes medication clinically proven to reduce the risk of cardiovascular death.

Jardiance received marketing approval in August 2014 for the treatment of patients with type 2 diabetes. In late 2016, Jardiance was further approved to reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease. In recent years,Eli Lilly- The Boehringer Ingelheim alliance has been committed to developing this drug for the treatment of heart failure and chronic kidney disease. Based on the results of the EMPEROR-Reduced trial, Jardiance was approved for a new indication in the European Union in June 2021 and in the United States in August 2021, respectively: for the treatment of adult patients with heart failure with reduced ejection fraction (HFrEF, systolic heart failure) to reduce the risk of cardiovascular death and hospitalization for heart failure, regardless of type 2 diabetes (T2D) status. Currently, the new indication for Jardiance in the treatment of HFrEF is also under review by China's National Medical Products Administration (NMPA). (Bioon.com)

Original Source:Jardiance shows consistent cardio-renal benefits in adults with heart failure with left ventricular ejection fraction over 40% regardless of chronic kidney disease status