CHMP Recommends Approval of Jardiance (Empagliflozin) for Treatment of Adults with Heart Failure with Reduced Ejection Fraction

May 24, 2021 News /BioonBIOON/ -- Boehringer Ingelheim andEli Lilly(Eli Lilly) recently jointly announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of the SGLT2 inhibitor Jardiance (Chinese trade name: Oupingtang, generic name: empagliflozin) for the treatment of adult patients with symptomatic chronic heart failure with reduced ejection fraction (HFrEF).

Currently, a supplemental new drug application (sNDA) for Jardiance is also under review by the U.S. FDA as a potential new treatment for adult patients with chronic heart failure with reduced ejection fraction (HFrEF), including those with and without type 2 diabetes.Diabetes mellitusof patients, reducing the risk of cardiovascular death and hospitalization for heart failure, and slowing the decline in renal function. Previously, the FDA granted Jardiance Fast Track designation (FTD) to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with HF. Additionally,FDAJardiance was also granted Fast Track Designation (FTD) for the treatment of chronic kidney disease (CKD).

Heart failure (HF) is a devastating and debilitating cardiovascular disease that not only impairs quality of life but is also a progressive disease requiring recurrent hospitalizations and accompanied by declining renal function.Primary endpoint results from the Phase 3 EMPEROR-Reduced trial showed that, in adult patients with HFrEF, when used in combination with standard of care,Compared with placebo, Jardiance significantly reduced the composite risk of cardiovascular death or hospitalization for heart failure by 25%.Results of the primary endpoint in patients with and without type 2Diabeteswere consistent in the (T2D) patient subgroup. Analysis of key secondary endpoints showed that,Jardiance reduced the relative risk of first and recurrent hospitalizations for heart failure by 30% and significantly slowed the decline in renal function.

HF affects over 60 million people globally, and a significant unmet medical need remains 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 is unable to 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 renal impairment, which may significantly 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 is unable to 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, resulting in less blood entering the heart compared to a normally functioning heart.

The EMPEROR-Reduced trial is part of the EMPOWER clinical program, which is the most extensive and comprehensive program among all SGLT2 inhibitors, and is exploring the impact of Jardiance on the lives of patients with cardiorenal-metabolic diseases.

The application for a new indication of Jardiance for the treatment of HFrEF is based on the results of the Phase III EMPEROR-Reduced trial (NCT03057977). This trial in adult patients with HFrEF (with or withoutDiabetes mellitus) was conducted, and the data showed that the study met its primary endpoint: when added to standard of care, compared with placebo, Jardiance 10 mg significantly reduced the risk of recurrent cardiovascular death or hospitalization for heart failure by 25%. The results were presented at the 2020 European Society of Cardiology (ESC) Congress and simultaneously published in The New England Journal of Medicine (NEJM). For details, see:Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure。

Results for the primary endpoint, in patients with and without type 2Diabeteswas consistent across patient subgroups. Analysis of key secondary endpoints in the trial demonstrated that, compared with placebo, Jardiance reduced the relative risk of first hospitalization and recurrent heart failure by 30%. In addition, the rate of decline in estimated glomerular filtration rate (eGFR), a marker of renal function deterioration, was slower in the Jardiance group than in the placebo group. In this trial, the safety profile of Jardiance was consistent with its known safety profile.

EMPEROR-Reduced Clinical Data

In an exploratory analysis, the absolute risk reduction observed for the primary endpoint of the EMPEROR-Reduced trial was equivalent to preventing one cardiovascular death or hospitalization for heart failure for every 19 patients treated for over 16 months. Another exploratory analysis demonstrated that Jardiance reduced the relative risk of a composite renal endpoint (including end-stage renal disease and severe renal function decline) by 50%.

In this trial, efficacy outcomes were achieved with a simple dosing regimen of once-daily administration without titration. The safety profile was consistent with the known safety profile of Jardiance. No clinically meaningful differences in adverse events were observed between Jardiance and placebo, including hypovolemia (reduced blood volume), hypotension, volume depletion (fluid loss), renal impairment (impaired kidney function), hyperkalemia (high potassium), and hypoglycemic events (low blood sugar).

Jardiance (Oupangjing, empagliflozin) belongs to the class of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Emerging SGLT-2 inhibitors have been demonstrated to block glucose reabsorption in the kidneys, excreting excess glucose from the body, thereby lowering blood glucose levels. Furthermore, this glucose-lowering effect is independent of β-cell function and insulin resistance.

In addition to its established glucose-lowering efficacy, this medication provides additional benefits including weight reduction, blood pressure lowering, and uric acid reduction. Jardiance demonstrates a favorable safety profile, reduces the risk of cardiovascular events in patients with diabetes, and is the first type 2 diabetes drug globally proven in clinical trials to reduce the risk of cardiovascular mortality.

Jardiance was approved for marketing in August 2014 for the treatment of patients with type 2 diabetes. In late 2016, Jardiance received additional approval to reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease. This approval made Jardiance the first glucose-lowering drug approved globally to reduce the risk of cardiovascular death in patients with type 2 diabetes.

Jardiance is a blockbuster SGLT2 inhibitor antidiabetic drug that currently accounts for over 50% of the market share among SGLT2 inhibitors. In recent years,Eli Lilly- The Boehringer Ingelheim alliance has been consistently committed to developing this drug for the treatment of heart failure and chronic kidney disease.

In China, Jardiance (欧唐静) received marketing approval in September 2017. It is indicated for use as monotherapy, in combination with metformin, or in combination with metformin and a sulfonylurea to improve glycemic control in patients with type 2 diabetes. In November 2019, Jardiance (欧唐静) was officially included in the National Reimbursement Drug List (NRDL). The NRDL officially took effect nationwide on January 1, 2020. With the nationwide implementation of the NRDL, it is expected that more Chinese patients with diabetes will benefit from this excellent therapeutic agent! (Bioon.com)

Original Source: CHMP issues positive opinion for Jardiance® (empagliflozin) for the treatment of adults with heart failure with reduced ejection fraction