ESC 2019: Novartis’ Entresto Shows Greater Clinical Benefit in Subgroups of Heart Failure with Preserved Ejection Fraction (HFpEF) Patients

September 02, 2019 News /BioonBIOON/ -- Swiss pharmaceutical giantNovartisNovartis recently announced the full results of the global Phase III clinical trial PARAGON-HF for its heart failure drug Entresto (Chinese brand name: Nuo Xin Tuo; sacubitril/valsartan). The study was conducted in patients with heart failure with preserved ejection fraction (HFpEF) to evaluate the efficacy and safety of Entresto compared with valsartan.

The results showed that, compared with valsartan, Entresto reduced the composite primary endpoint of total heart failure hospitalizations (first and recurrent) and cardiovascular (CV) death by 13% (p=0.059), a finding primarily driven by a nearly 15% reduction in the total number of heart failure hospitalizations (first and recurrent) (p=0.056).

HFpEF is a heterogeneous form of heart failure for which no drugs have yet been approved. Although the primary endpoint data missed statistical significance, butAll evidence from the study indicates that Entresto may provide clinically significant benefits in specific subgroups of patients with HFpEF. Pre-specified subgroup analyses demonstrated a greater treatment effect in individuals with left ventricular ejection fraction ≤ the median of 57% (22% reduction in the primary endpoint; 95% CI: 0.641–0.949) and in female patients (27.5% reduction in the primary endpoint; 95% CI: 0.588–0.895). The safety and tolerability profile of Entresto in this study was consistent with previously reported findings in patients with HFrEF.

Currently, Entresto is an essential medication approved for the treatment of patients with heart failure with reduced ejection fraction (HFrEF), typically defined as an ejection fraction <40%. The full results of the PARAGON-HF study were recently presented at the 2019 annualConferencepublished above.

Dr. David Soergel, Global Head of Cardiovascular, Renal and Metabolism Drug Development at Novartis Pharmaceuticals, stated: “Novartis is proud of its significant contribution to the scientific evidence in the field of HFpEF through the PARAGON-HF study. This study underscores the critical need for therapeutic options for this complex disease.”Novartis“Committed to reshaping the treatment of heart failure, our next step is to further explore the results from the PARAGON-HF study. We also look forward to continuing discussions with clinical experts and regulatory authorities to determine the next steps.”

Scott Solomon, Co-Chair of the PARAGON-HF Executive Committee, Professor at Harvard Medical School, and Director of the Non-Invasive Cardiac Imaging Program at Brigham and Women’s Hospital, stated: “Although the reduction in the primary endpoint was not statistically significant, the totality of evidence from PARAGON-HF suggests that Entresto offers potential overall benefits compared with valsartan in patients with heart failure with preserved ejection fraction (HFpEF), particularly in those with ejection fractions below the normal range. This also underscores the complexity of HFpEF, indicating that certain therapies may have a more pronounced effect in specific patient subgroups, including women, who are more susceptible to this condition than men.”

Heart failure (HF) is a progressive and severe disease affecting approximately 26 million people worldwide, in which the heart is unable to pump sufficient blood to the body. There are two distinct types: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).

Among these, HFpEF is a distinct type of heart failure in which the myocardium contracts normally, but the ventricles fail to relax properly during ventricular filling (or ventricular relaxation). HFpEF is associated with high hospitalization rates, poor quality of life, and increased mortality, and is gradually becoming the predominant form of heart failure; currently, there are no approved pharmacological treatments. HFrEF indicates insufficient cardiac contractility, resulting in reduced blood ejection, and approved therapeutic agents are currently available.

Entresto is a dual-acting angiotensin receptor-neprilysin inhibitor (ARNI) with a unique mode of action that enhances the heart’s protective neuroendocrine system (the NP system, or natriuretic peptide system) while inhibiting the harmful system (the RAAS system, or renin-angiotensin-aldosterone system), and is considered to reduce strain on the failing heart. Entresto combinesNovartisHypertensionDiovan (generic name: valsartan) and sacubitril, the latter being a neprilysin inhibitor that blocks the mechanisms of two peptides responsible for lowering blood pressure, while valsartan is an angiotensin II receptor antagonist that improves vasodilation and stimulates the excretion of sodium and water.

Since its approval in July 2015 for the treatment of heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and heart failure hospitalization, Entresto has become a preferred and foundational therapy for HFrEF. Entresto acts on the cardiac neuroendocrine system through multiple mechanisms and is regarded as a major breakthrough in heart failure treatment over the past two decades. It was the first drug to demonstrate significantly superior efficacy compared to the standard-of-care medication enalapril in clinical studies, substantially reducing cardiovascular death and heart failure hospitalizations while exhibiting a favorable safety profile. As such, it represents one of the most significant advances in cardiology in the past decade.

In the Chinese market, Entresto (Novartis) was approved in July 2017 for adult patients with chronic heart failure with reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization due to heart failure.

In 2018, global sales of Entresto reached $1.028 billion, representing a 103% increase compared to 2017. Recently, Novartis released its financial report for the first half of 2019, which showed that Entresto’s sales amounted to $778 million, an 83% year-over-year increase. The drug has become a driving force behindNovartisA key product driving sales growth. (Bioon.com)

Original Source:Novartis