Novartis' Heart Failure Drug Entresto Receives FDA Advisory Committee Support (12-1 Vote) for Expanded Use in HFpEF

Novartis recently announced that the U.S. FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 12 to 1 in favor of using Entresto (sacubitril/valsartan; Chinese brand name: Nuo Xin Tuo) for the treatment of patients with heart failure with preserved ejection fraction (HFpEF). The press release noted that, if approved by the FDA, Entresto would become the first therapy approved for HFpEF patients and the first drug approved for the treatment of both major types of chronic heart failure.

HFpEF affects more than 3 million Americans, and its prevalence is increasing with the aging of the population. Despite decades of research, developing effective treatments remains challenging due to the heterogeneity of its pathophysiology and the variable impact of patient symptoms. HFpEF can alter cardiac structure; it occurs when the heart muscle thickens and stiffens, impairing its ability to relax and fill with sufficient blood to meet the body’s needs. HFpEF is associated with high rates of hospital readmission for heart failure, emergency department visits, and urgent physician appointments. Each hospitalization event is linked to worsening long-term prognosis, with approximately one-quarter of patients being readmitted for heart failure within one year after discharge.

Entresto has been approved in 115 countries worldwide for the treatment of heart failure with reduced ejection fraction (HFrEF). In China, it was approved for marketing in 2017. Entresto combines the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan, a combination that enhances therapeutic benefits. On one hand, sacubitril augments the beneficial effects of the natriuretic peptide system, promoting natriuresis and diuresis, vasodilation, and cardioprotection. On the other hand, valsartan inhibits the renin-angiotensin-aldosterone system (RAAS), leading to vasodilation, improved sodium and water retention, and reduced cardiac load.

The Committee’s positive decision was based on an analysis of comprehensive data on the efficacy and safety of Entresto, including data from the Phase 3 clinical trial PARAGON-HF and the Phase 2 clinical trial PARAMOUNT conducted in patients with heart failure with preserved ejection fraction (HFpEF), as well as data from Phase 3 clinical trials in patients with heart failure with reduced ejection fraction (HFrEF). The PARAGON-HF data demonstrated a favorable safety profile of Entresto in patients with HFpEF, consistent with extensive clinical and post-marketing experience in patients with HFrEF, and showed the clinical benefit of Entresto in patients with HFpEF.

References:

[1] Novartis announces positive FDA Advisory Committee recommendation for use of Entresto® to treat patients with HFpEF. Retrieved December 16, 2020, from https://www.novartis.com/news/media-releases/novartis-announces-positive-fda-advisory-committee-recommendation-use-entresto-treat-patients-hfpef

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