Novartis’ Entresto Demonstrates Improvement in Cardiac Structure and Function in HFrEF Patients, According to PROVE-HF and EVALUATE-HF Trials Presented at ESC 2019

September 03, 2019 News /Bio ValleyBIOON/ -- Swiss pharmaceutical giantNovartis(Novartis) recently announced the results of two new clinical studies, PROVE-HF and EVALUATE-HF. These studies were conducted in patients with heart failure with reduced ejection fraction (HFrEF) to evaluate the improvement in cardiac structure and function as well as long-term safety of the heart failure medication Entresto (Chinese brand name: Nuoxintuo; sacubitril/valsartan). The results showed that, as a foundational therapy for HFrEF, Entresto not only affects prognostic clinical outcomes associated with HFrEFBiomarkersexerted a positive impact, and these effects were associated with significant improvements in cardiac structural and functional changes (i.e., cardiac remodeling). The safety and tolerability profiles in these studies were consistent with those reported previously.

Cardiac remodeling can impair the heart’s ability to pump blood to the body, leading to poor prognosis. Therefore, positively influencing cardiac remodeling may be important in the treatment of HFrEF, as it may lead to reversal of cardiac damage and thereby improve clinical outcomes. These data demonstrate for the first time that Entresto improves cardiac structure and function, indicating reversal of cardiac remodeling, and that this improvement is associated with favorable changes in biomarkers. These results further support Entresto as the preferred treatment for HFrEF; detailed data were presented at the European Society of Cardiology (ESC) 2019 Annual Congress held recently.Meetingpublished in the Journal of the American Medical Association (JAMA).

PROVE-HF is a Phase IV, 52-week, single-arm, open-label study demonstrating that treatment with Entresto significantly improved levels of an important biomarker associated with clinical outcomes in HFrEF—N-terminal pro-B-type natriuretic peptide (NT-proBNP). This is theBiomarkersIt was the first to demonstrate a significant association with reverse left ventricular remodeling and improved echocardiographic measures of cardiac structure and function. Importantly, this study confirmed the association between improvements in this biomarker and these favorable changes in reverse cardiac remodeling at 6 months and 1 year. The study found that, apart from dizziness, the safety and tolerability profile of Entresto was largely consistent with that observed in the pivotal PARADIGM-HF trial, whereas dizziness was more frequently reported in the PROVE-HF study.

The EVALUATE-HF study was a Phase IV, multicenter, randomized, double-blind, active-controlled study comparing the effects of Entresto and enalapril on cardiovascular remodeling and ventriculo-arterial coupling (a measure of cardiac mechanical efficiency). Presented at the 2019 ESC Congress, the study results showed that neither Entresto nor enalapril improved the primary endpoint of changes in aortic impedance (a measure of arterial stiffness). The short duration of the study and the specific patient population (who may have already experienced some degree of improvement in aortic impedance) may have contributed to this outcome. However, consistent with the findings of the PROVE-HF study, it demonstrated that Entresto improved the structure and function of the left ventricle (the chamber that pumps blood to the rest of the body) compared to enalapril, with a safety profile similar to that observed in the PARADIGM-HF study.

NovartisMarcia Kayath, M.D., Global Head of Medical Affairs and Chief Medical Officer at Novartis, stated: “

The PROVE-HF and EVALUATE-HF studies provided the first evidence demonstrating that Entresto may help reverse cardiac damage caused by HFrEF, thereby improving clinical outcomes. As part of our commitment to transforming heart failure treatment, we conducted these studies to gain a deeper understanding of the impact of Entresto on cardiac structure and function in patients with HFrEF. This is the first time an association has been shown between biomarkers and improved cardiac remodeling in patients receiving Entresto therapy.”

Heart failure (HF) is a progressive and severe disease affecting approximately 26 million people worldwide, characterized by the heart's inability to pump sufficient blood to the body. There are two distinct types of HF: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). HFpEF is a unique form of heart failure in which the myocardium contracts normally, but the ventricles fail to relax properly during ventricular filling (or diastole). HFpEF is associated with high hospitalization rates, poor quality of life, and increased mortality, and is increasingly becoming the predominant form of HF; currently, there are no approved pharmacological treatments for this condition. In contrast, HFrEF indicates insufficient contractile force of the heart, resulting in reduced blood output, and there are approved therapeutic agents available for its treatment.

Entresto is a dual-acting angiotensin receptor-neprilysin inhibitor (ARNI) with a unique mechanism 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 combinesNovartisHypertensionThe medications Diovan (generic name: valsartan) and sacubitril, the latter being a neprilysin inhibitor that blocks the mechanism of action of two peptides responsible for lowering blood pressure; 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 hospitalization for heart failure, Entresto has become a preferred and foundational therapy for HFrEF. By modulating the cardiac neuroendocrine system through multiple mechanisms, Entresto 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 agent enalapril in clinical trials, substantially reducing cardiovascular death and heart failure hospitalizations while exhibiting an improved safety profile. As such, it represents one of the most important 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 for heart failure.

In 2018, global sales of Entresto reached $1.028 billion, representing a year-over-year growth of 103% 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% increase from the same period last year. The drug has become a driving force behindNovartisA key product driving sales growth. (Bioon.com)

Original Source:Novartis