Novartis has announced that its heart failure with reduced ejection fraction (HFrEF) drug Entresto (sacubitril/valsartan) has shown further efficacy in two Phase IV trials, PROVE-HF and EVALUATE-HF.
In the PARADIGM-HF study that led to its approval in 2015, Entresto showed superiority to standard-of-care angiotensin-converting enzyme (ACE) inhibitor enalapril.
However, this latest Phase IV data shows that the drug also significantly improves the structural and functional changes that occur during heart failure, which is known as cardiac remodelling, as well as causing positive changes in an important biomarker, N-terminal pro–B-type natriuretic peptide (NT-proBNP). This means that Entresto’s use may reverse damage to the heart in HFrEF patients.
This announcement was made at the European Society of Cardiology Congress in Paris over the weekend; the results from the two studies were published in the Journal of the American Medical Association.
Novartis chief medical officer and global head of medical affairs Marcia Kayath said: "The PROVE-HF and EVALUATE-HF studies provide the first evidence that Entresto may help reverse the damage to the heart caused by HFrEF, which could lead to improved clinical outcomes.
"As part of our commitment to reimagining heart failure treatment, we conducted these studies to more deeply understand Entresto’s impact on heart structure and function in HFrEF patients.
"For the first time, an association was shown between a biomarker and cardiac remodelling improvements in patients treated with Entresto."
In the PROVE-HF trial, Entresto significantly improved the levels of NT-proBNP, which is associated with good clinical outcomes in HFrEF. This was linked with significant improvement in left ventricular remodelling and echocardiographic measures of cardiac structure and function.
Novartis’s drug improved the structure and function of the left ventricle, compared to enalparil, in the EVALUATE-HF study, but both arms of the study failed to cause a change in aortic impedance, the primary endpoint of the study.
The safety and tolerability of the drug in these two trials was consistent with Entresto’s profile from the PARADIGM-HF study.
Despite improved efficacy in HFrEF patients, Entresto failed to meet its primary endpoint in the Phase III PARAGON-HF study of heart failure patients with preserved ejection fraction (HFpEF).
Although Novartis’s drug reduced the total heart failure hospitalisations and cardiovascular deaths by 13%, this result was not statistically significant.
Novartis global head of cardiovascular, renal and metabolic drug development David Soergel commented: "Novartis is committed to reimagining heart failure treatment, and our next step is to further explore these results from PARAGON-HF.
"We also look forward to continuing conversations with clinical experts and regulators to determine next steps."
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