CLINICAL TRIALS PROFILE FOR SACUBITRIL AND VALSARTAN

All Clinical Trials for SACUBITRIL AND VALSARTAN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01920711 ↗	Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction	Completed	Novartis Pharmaceuticals	Phase 3	2014-07-18	The purpose of this study was to evaluate the effect of LCZ696 compared to valsartan in the reduction of cardiovascular death and heart failure(HF) hospitalizations in patients with HF with preserved ejection fraction.
NCT02554890 ↗	Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode.	Completed	Novartis Pharmaceuticals	Phase 4	2016-04-29	The purpose of this study was to assess the effect of in-hospital initiation of sacubitril/valsartan (LCZ696) vs. enalapril on time averaged proportional change in NT-proBNP in patients who have been stabilized following hospitalization for acute decompensated heart failure (ADHF) and reduced ejection fraction (left ventricular ejection fraction (LVEF) ≤ 40%).
NCT02636283 ↗	Use of Entresto Sacubitril/Valsartan for the Treatment of Peripheral Arterial Disease	Terminated	American Heart Association	Phase 2	2017-12-31	This study proposes the use of Entresto (sacubitril/valsartan) to test the effects on pain free walking duration on patients with peripheral arterial disease, a condition caused by decreased blood flow to the muscles in the legs.
NCT02636283 ↗	Use of Entresto Sacubitril/Valsartan for the Treatment of Peripheral Arterial Disease	Terminated	University of Minnesota	Phase 2	2017-12-31	This study proposes the use of Entresto (sacubitril/valsartan) to test the effects on pain free walking duration on patients with peripheral arterial disease, a condition caused by decreased blood flow to the muscles in the legs.
NCT02636283 ↗	Use of Entresto Sacubitril/Valsartan for the Treatment of Peripheral Arterial Disease	Terminated	University of Minnesota - Clinical and Translational Science Institute	Phase 2	2017-12-31	This study proposes the use of Entresto (sacubitril/valsartan) to test the effects on pain free walking duration on patients with peripheral arterial disease, a condition caused by decreased blood flow to the muscles in the legs.
NCT02682719 ↗	Personalised Prospective Comparison of ARni With ArB in Patients With Natriuretic Peptide eLEvation	Active, not recruiting	Novartis Ireland Ltd	Phase 2	2015-12-16	Sacubitril-valsartan, an Angiotensin Receptor Blocker-Neprilysin Inhibitor (ARNI), currently marketed for the management of heart failure, has been shown to reduce cardiovascular morbidity and mortality in stage C heart failure with reduced ejection fraction. In stage C HFpEF, sacubitril-valsartan has also been shown to reduce left atrial volume index measured using echocardiography over a 9 month timeframe. The PARABLE study investigates the hypothesis that sacubitril-valsartan can provide benefits in terms of left atrial structure and function as well as left ventricular structure and function in asymptomatic (stage A/B HFpEF) patients. This is a prospective, randomised, double-blind, double-dummy, phase II study design. The patient population will have hypertension and/or diabetes together with preserved ejection fraction, elevated natriuretic peptide (NP) and abnormal left atrial volume index (LAVI, > 28 mL/m2).
NCT02682719 ↗	Personalised Prospective Comparison of ARni With ArB in Patients With Natriuretic Peptide eLEvation	Active, not recruiting	The Heartbeat Trust	Phase 2	2015-12-16	Sacubitril-valsartan, an Angiotensin Receptor Blocker-Neprilysin Inhibitor (ARNI), currently marketed for the management of heart failure, has been shown to reduce cardiovascular morbidity and mortality in stage C heart failure with reduced ejection fraction. In stage C HFpEF, sacubitril-valsartan has also been shown to reduce left atrial volume index measured using echocardiography over a 9 month timeframe. The PARABLE study investigates the hypothesis that sacubitril-valsartan can provide benefits in terms of left atrial structure and function as well as left ventricular structure and function in asymptomatic (stage A/B HFpEF) patients. This is a prospective, randomised, double-blind, double-dummy, phase II study design. The patient population will have hypertension and/or diabetes together with preserved ejection fraction, elevated natriuretic peptide (NP) and abnormal left atrial volume index (LAVI, > 28 mL/m2).

Clinical Trial Conditions for SACUBITRIL AND VALSARTAN

Condition Name

Condition Name for SACUBITRIL AND VALSARTAN
Intervention	Trials
Heart Failure	32
Hypertension	8
Heart Failure With Preserved Ejection Fraction	7
Cardiotoxicity	3

Condition MeSH

Condition MeSH for SACUBITRIL AND VALSARTAN
Intervention	Trials
Heart Failure	60
Hypertension	7
Myocardial Infarction	6
Infarction	5

Clinical Trial Locations for SACUBITRIL AND VALSARTAN

Trials by Country

Trials by Country for SACUBITRIL AND VALSARTAN
Location	Trials
United States	267
Italy	53
Spain	50
Japan	47
China	36

Trials by US State

Trials by US State for SACUBITRIL AND VALSARTAN
Location	Trials
California	11
Massachusetts	10
Virginia	10
Tennessee	10
Florida	9

Clinical Trial Progress for SACUBITRIL AND VALSARTAN

Clinical Trial Phase

Clinical Trial Phase for SACUBITRIL AND VALSARTAN
Clinical Trial Phase	Trials
Phase 4	40
Phase 3	16
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for SACUBITRIL AND VALSARTAN
Clinical Trial Phase	Trials
Recruiting	37
Completed	21
Not yet recruiting	19

Clinical Trial Sponsors for SACUBITRIL AND VALSARTAN

Sponsor Name

Sponsor Name for SACUBITRIL AND VALSARTAN
Sponsor	Trials
Novartis Pharmaceuticals	22
Brigham and Women's Hospital	4
The Heartbeat Trust	3

Sponsor Type

Sponsor Type for SACUBITRIL AND VALSARTAN
Sponsor	Trials
Other	120
Industry	30
NIH	4

SACUBITRIL AND VALSARTAN Market Analysis and Financial Projection

Sacubitril and Valsartan: Clinical Trials, Market Analysis, and Projections

Introduction

Sacubitril and valsartan, a combination drug marketed under the name Entresto, has been a significant advancement in the treatment of heart failure with reduced ejection fraction (HFrEF). This article delves into the recent clinical trials, market analysis, and future projections for this medication.

Clinical Trials Overview

PARADIGM-HF and PARAGON-HF Trials

The PARADIGM-HF and PARAGON-HF trials are pivotal in understanding the efficacy of sacubitril/valsartan. These trials involved a large cohort of patients with chronic heart failure and compared sacubitril/valsartan with renin-angiotensin system inhibitors (RASi) such as enalapril and valsartan.

• PARADIGM-HF Trial: This trial focused on patients with an left ventricular ejection fraction (LVEF) of 40% or less. It demonstrated that sacubitril/valsartan significantly reduced the risk of all-cause hospitalization, primarily driven by lower rates of cardiac and pulmonary hospitalizations[4].
• PARAGON-HF Trial: This trial included patients with an LVEF of 45% or greater. The pooled analysis of both trials showed consistent benefits of sacubitril/valsartan in reducing hospitalizations across the spectrum of LVEF[4].

LIFE Trial

The LIFE trial, a 24-week prospective, multicenter, randomized, double-blind, double-dummy, active comparator phase 4 clinical trial, assessed the tolerability, safety, and efficacy of sacubitril/valsartan compared with valsartan in patients with advanced chronic heart failure and recent New York Heart Association (NYHA) class IV symptoms. The trial found no significant difference between sacubitril/valsartan and valsartan in lowering NT-proBNP levels, although it highlighted the challenges of tolerability and adherence to sacubitril/valsartan[1].

Efficacy and Safety

Reduction in Hospitalizations

The post hoc pooled analysis of the PARADIGM-HF and PARAGON-HF trials clearly indicates that sacubitril/valsartan reduces the risk of all-cause hospitalizations, particularly those related to cardiac and pulmonary issues. This reduction is a critical factor in improving patient outcomes and reducing healthcare costs[4].

Tolerability and Safety

The LIFE trial highlighted that while sacubitril/valsartan is effective, it may not be well-tolerated by all patients. Approximately 18% of patients were unable to tolerate the drug during the short run-in period, and 29% discontinued it during the 24-week trial. This suggests that careful patient selection and monitoring are essential[1].

Cost-Effectiveness Analysis

Comparison with Enalapril

Studies have shown that sacubitril/valsartan is more effective than enalapril in terms of reducing mortality and improving quality-adjusted life-years (QALYs). However, the cost-effectiveness varies by region and healthcare system. In Thailand, for example, the incremental cost-effectiveness ratio (ICER) of sacubitril/valsartan compared to enalapril was found to be high, suggesting it may not be cost-effective at current prices[2].

Economic Value

An updated economic evaluation using participant-level clinical trial data indicated that sacubitril/valsartan provides high economic value for patients with reduced and mildly reduced ejection fractions (≤50%) and at least intermediate value at an ejection fraction of 60% or lower. This analysis supports the inclusion of sacubitril/valsartan in clinical practice guidelines due to its cost-effectiveness, especially at lower ejection fractions[5].

Market Analysis

Current Market Position

Sacubitril/valsartan has been recommended as a replacement for enalapril in the treatment of HFrEF, reflecting its clinical superiority. However, its adoption is influenced by cost considerations, particularly in regions with limited healthcare resources.

Pricing and Accessibility

The cost of sacubitril/valsartan is a significant factor in its market penetration. In some countries, the drug is not considered cost-effective at its current price, highlighting the need for price adjustments or subsidies to make it more accessible[2].

Future Projections

Expanding Indications

Future clinical trials may explore the use of sacubitril/valsartan in other heart failure populations, such as those with preserved ejection fraction or specific comorbidities. This could expand its market potential and further solidify its position in heart failure treatment.

Cost Reduction Strategies

To improve cost-effectiveness, manufacturers may need to reduce the price of sacubitril/valsartan or negotiate better pricing with healthcare systems. This could involve discounts, value-based pricing models, or other strategies to make the drug more affordable.

Regulatory and Reimbursement Decisions

Regulatory bodies and healthcare payers will continue to evaluate the cost-effectiveness and clinical benefits of sacubitril/valsartan. Positive evaluations could lead to broader coverage and reimbursement, enhancing its market presence.

Key Takeaways

• Clinical Efficacy: Sacubitril/valsartan has been shown to reduce hospitalizations and improve outcomes in patients with HFrEF.
• Cost-Effectiveness: While the drug is more effective than traditional treatments, its cost-effectiveness varies by region and healthcare system.
• Market Position: The drug's adoption is influenced by its clinical superiority and cost considerations.
• Future Directions: Expanding indications, cost reduction strategies, and favorable regulatory decisions could further enhance its market position.

FAQs

What is the primary benefit of sacubitril/valsartan in heart failure treatment?

The primary benefit of sacubitril/valsartan is its ability to reduce the risk of all-cause hospitalizations, particularly those related to cardiac and pulmonary issues.

How does the cost-effectiveness of sacubitril/valsartan compare to enalapril?

Sacubitril/valsartan is more effective than enalapril but may not be cost-effective at current prices in some regions, such as Thailand.

What are the main challenges in the adoption of sacubitril/valsartan?

The main challenges include tolerability issues, high costs, and varying cost-effectiveness across different healthcare systems.

Are there ongoing or planned clinical trials to expand the indications of sacubitril/valsartan?

Yes, future trials may explore the use of sacubitril/valsartan in other heart failure populations, potentially expanding its market.

How might the cost of sacubitril/valsartan be made more manageable for healthcare systems?

Manufacturers could reduce the price, negotiate better pricing, or implement value-based pricing models to make the drug more affordable.

Sources

1. JAMA Cardiology: "Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Chronic Heart Failure and Recent New York Heart Association Class IV Symptoms: The LIFE Randomized Clinical Trial"[1]
2. PubMed: "Cost-Effectiveness Analysis of Sacubitril-Valsartan Compared with Enalapril in Patients with Heart Failure with Reduced Ejection Fraction in Thailand"[2]
3. Value in Health: "Cost-Effectiveness of Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction"[3]
4. JAMA Cardiology: "Effects of Sacubitril/Valsartan on All-Cause Hospitalizations in Heart Failure: Post Hoc Analysis of the PARADIGM-HF and PARAGON-HF Randomized Clinical Trials"[4]
5. JAMA Cardiology: "Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure with Reduced Ejection Fraction"[5]