ENTRESTO (sacubitril)
Entresto is a combination medication indicated to reduce the risk of cardiovascular death and hospitalization in adults with chronic heart failure. The drug is also approved for the treatment of symptomatic heart failure in pediatric patients aged one year and older who have systemic left ventricular systolic dysfunction. In adult populations, therapeutic benefits are most clearly evident in patients with a left ventricular ejection fraction below normal. The treatment is expected to improve cardiovascular outcomes and has been shown to reduce NT-proBNP levels.
How ENTRESTO Works
Entresto functions through the dual action of a neprilysin inhibitor, sacubitril, and an angiotensin II receptor blocker, valsartan. Sacubitril’s active metabolite inhibits the enzyme neprilysin, which increases levels of beneficial peptides, such as natriuretic peptides, that are normally degraded by that enzyme. Simultaneously, valsartan selectively blocks the angiotensin II type-1 receptor, which inhibits the vasoconstrictive effects of angiotensin II and the release of aldosterone. These combined mechanisms result in cardiovascular and renal effects that assist in the management of heart failure.
Development Insights
Details
- Status
- Prescription
- First Approved
- 2015-07-07
- Patent Cliff
- 2036
- Revenue
- $1.3B (Q4-2025)
- Routes
- ORAL
- Dosage Forms
- TABLET
ENTRESTO Approval History
What ENTRESTO Treats
2 indicationsENTRESTO is approved for 2 conditions since its original approval in 2015. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Chronic heart failure in adults
- Symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older
ENTRESTO Boxed Warning
FETAL TOXICITY When pregnancy is detected, discontinue ENTRESTO as soon as possible (5.1) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (5.1) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue ENTRESTO as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 )...
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue ENTRESTO as soon as possible (5.1) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (5.1) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue ENTRESTO as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 )
ENTRESTO Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
Direct competitors
Same target(s) AND same indication — head-to-head.
MoA expansion candidates
Same target(s), different indications — where else is this mechanism being explored?
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
Clinical Trial Registry
6 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT03553810 REVERSE-LVH | 2018/2182 | Ph 2 | completed | Role of ARNi in Ventricular Remodeling in Hypertensive LVH |
| NCT03279861 | HP-00076889 | Ph 4 | withdrawn | Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD |
| NCT03893526 NEPT2D | NEPT2D | Ph 4 | completed | Effect of Neprilysin on Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes |
| NCT02754518 results posted | IRB15-1410 | Ph 4 | completed | Demonstration of Reverse Remodeling Effects of Entresto. Using Echocardiography Endocardial Surface Analysis |
| NCT02636283 results posted | 15SDG25360025 | Ph 2 | terminated | Use of Entresto Sacubitril/Valsartan for the Treatment of Peripheral Arterial Disease |
| NCT03717688 NEP | NEP and GLP-1 | Ph 4 | completed | The Effects of Neprilysin on Glucagon-like Peptide-1 |
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
ENTRESTO FDA Label Details
Indications & Usage
FDA Label (PDF)ENTRESTO is indicated for the treatment of Chronic heart failure in adults; Symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue ENTRESTO as soon as possible (5.1) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (5.1) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. Whe...
ENTRESTO Patents & Exclusivity
Patents (8 active)
Pro Intelligence Preview
Deep insights for ENTRESTO
Revenue Insights
- • Q4-2025: $1.3B
- • Historical trend analysis
Patent Timeline
- • Cliff: 2036
- • 72 active patents
Trial Analysis
- • 6 total trials
- • Stage: Mature
Competitive Landscape
- • Competitor tracking
- • Same target/indication analysis
Full approval history • All patents • Revenue trends • Competitor analysis
Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.
How We Calculate These Metrics
Trial Activity Stage
Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.
Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.
- Growth: High proportion of early-phase trials (Phase 1/2), active development
- Expansion: Significant Phase 3 activity, approaching or pursuing approvals
- Mature: Substantial Phase 4 post-marketing studies
- Stable: Mixed phase distribution, steady development
- Declining: Low active trial ratio, reduced R&D investment