ENTRESTO Drug Patent Profile

Which patents cover Entresto, and what generic alternatives are available?

Entresto is a drug marketed by Novartis Pharms Corp and Novartis and is included in two NDAs. There are eleven patents protecting this drug and one Paragraph IV challenge.

This drug has one hundred and eighty patent family members in forty-four countries.

The generic ingredient in ENTRESTO is sacubitril; valsartan. There are eleven drug master file entries for this compound. Twenty-one suppliers are listed for this compound. Additional details are available on the sacubitril; valsartan profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Entresto

A generic version of ENTRESTO was approved as sacubitril; valsartan by ALEMBIC on May 28^th, 2024.

Summary for ENTRESTO

International Patents:	180
US Patents:	7
Applicants:	2
NDAs:	2
Finished Product Suppliers / Packagers:	2
Raw Ingredient (Bulk) Api Vendors:	1
Clinical Trials:	45
Patent Applications:	166
Drug Prices:	Drug price information for ENTRESTO
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for ENTRESTO
What excipients (inactive ingredients) are in ENTRESTO?	ENTRESTO excipients list
DailyMed Link:	ENTRESTO at DailyMed

See drug prices for ENTRESTO

Recent Clinical Trials for ENTRESTO

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Humanis Saglk Anonim Sirketi	PHASE1
Bio-innova Co., Ltd	PHASE1
Viatris Inc.	PHASE1

See all ENTRESTO clinical trials

Pharmacology for ENTRESTO

Drug Class	Angiotensin 2 Receptor Blocker Neprilysin Inhibitor
Mechanism of Action	Angiotensin 2 Receptor Antagonists Neprilysin Inhibitors

Paragraph IV (Patent) Challenges for ENTRESTO

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
ENTRESTO	Tablets	sacubitril; valsartan	24 mg/26 mg, 49 mg/51 mg 97 mg/103 mg	207620	18	2019-07-08

US Patents and Regulatory Information for ENTRESTO

ENTRESTO is protected by seven US patents.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-002	Apr 12, 2024		RX	Yes	Yes	8,877,938		Y	Y
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-002	Apr 12, 2024		RX	Yes	Yes	8,101,659		Y
Novartis Pharms Corp	ENTRESTO	sacubitril; valsartan	TABLET;ORAL	207620-001	Jul 7, 2015	AB	RX	Yes	No	11,135,192
Novartis Pharms Corp	ENTRESTO	sacubitril; valsartan	TABLET;ORAL	207620-003	Jul 7, 2015	AB	RX	Yes	Yes	11,058,667

EU/EMA Drug Approvals for ENTRESTO

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Novartis Europharm Limited	Neparvis	sacubitril, valsartan	EMEA/H/C/004343Paediatric heart failureNeparvis is indicated in children and adolescents aged one year or older for treatment of symptomatic chronic heart failure with left ventricular systolic dysfunction (see section 5.1).Adult heart failureNeparvis is indicated in adult patients for treatment of symptomatic chronic heart failure with reduced ejection fraction (see section 5.1).	Authorised	no	no	no	2016-05-26
Novartis Europharm Limited	Entresto	sacubitril, valsartan	EMEA/H/C/004062Paediatric heart failureEntresto is indicated in children and adolescents aged one year or older for treatment of symptomatic chronic heart failure with left ventricular systolic dysfunction.Adult heart failureEntresto is indicated in adult patients for treatment of symptomatic chronic heart failure with reduced ejection fraction.	Authorised	no	no	no	2015-11-19

International Patents for ENTRESTO

When does loss-of-exclusivity occur for ENTRESTO?

Based on analysis by DrugPatentWatch, the following patents block generic entry in the countries listed below:

Croatia

Cyprus

Denmark

European Patent Office

Finland

Hungary

Japan

Lithuania

Poland

Portugal

Serbia

Slovenia

Spain

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

See the table below for additional patents covering ENTRESTO around the world.

Country	Patent Number	Title	Estimated Expiration
China	102702119	Pharmaceutical combinations of an angiotensin receptor antagonist and an NEP inhibitor
Mexico	2015002432	INHIBIDORES DE LA NEP PARA EL TRATAMIENTO DE ENFERMEDADES CARACTERIZADAS POR EL ENSANCHAMIENTO O REMODELACION AURICULAR. (NEP INHIBITORS FOR TREATING DISEASES CHARACTERIZED BY ATRIAL ENLARGEMENT OR REMODELING.)
Poland	2887961
Mexico	378867

Supplementary Protection Certificates for ENTRESTO

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1948158	1690020-1	Sweden		PRODUCT NAME: SACUBITRIL AND VALSARTAN, AS SACUBITRIL VALSARTAN SODIUM SALT COMPLEX, I.E. TRISODIUM 3-((1S,3R)-1-BIPHENYL-4-YLMETHYL-3- ETHOXYCARBONYL-1-BUTYLCARBAMOYL)PROPIONATE-(S)-3-METHYL-2- (PENTANOYL2-(TETRAZOL-5-YLATE)BIPHENYL-4- YLMETHYLAMINO)BUTYRATE HEMIPENTAHYDRATE; REG. NO/DATE: EU/1/15/1058 20151123
1467728	132016000051059	Italy		PRODUCT NAME: SACUBITRIL/VALSARTAN, INCLUSI LORO SALI FARMACEUTICAMENTE ACCETTABILI(ENTRESTO); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/15/1058 - C(2015)8288, 20151123
2340828	2021C/502	Belgium		PRODUCT NAME: SACUBITRIL/VALSARTAN, ALS HET SACUBITRIL VALSARTAN NATRIUMZOUTCOMPLEX, I.E. (((S)-N-VALERYL-N-((2'-(1H-TETRAZOL-5-YL)-BIFENYL-4-YL)-METHYL)-VALINE) ((2R,4S)-5-BIFENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-PENTAANZUURETHYLESTER))NA3 . X H2O, WAARBIJ X 0 TOT 3 IS; AUTHORISATION NUMBER AND DATE: EU/1/15/1058 (C(2015) 8288) 20151123
1467728	1690021-9	Sweden		PRODUCT NAME: SACUBITRIL AND VALSARTAN, INCLUDING PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF.; REG. NO/DATE: EU/1/15/1058 20151123

Market Dynamics and Financial Trajectory for ENTRESTO

Last updated: November 7, 2025

Introduction

ENTRESTO (sacubitril/valsartan), marketed by Novartis, has redefined the management of heart failure with reduced ejection fraction (HFrEF). Since its FDA approval in 2015, ENTRESTO's market penetration, clinical efficacy, and evolving competitive landscape have significantly shaped its commercial and financial trajectory. This report analyzes the core drivers underpinning its market dynamics and projects its future financial outlook.

Market Landscape and Therapeutic Context

HFrEF remains a prevalent cardiovascular disorder, affecting over 26 million individuals globally [1]. Conventional treatments include ACE inhibitors, ARBs, beta-blockers, and mineralocorticoid receptor antagonists, yet persistent high morbidity and mortality underscore unmet needs. ENTRESTO's dual mechanism—combining neprilysin inhibition with angiotensin receptor blockade—offers enhanced therapeutic benefits, including reduced hospitalizations and mortality [2].

In 2015, the FDA approved ENTRESTO based on the PARADIGM-HF trial, which demonstrated a 20% relative risk reduction in cardiovascular death and heart failure hospitalization compared to enalapril [3]. Subsequent guidelines increasingly favor its use, fueling market penetration.

Market Adoption Drivers

Clinical Efficacy and Regulatory Endorsements

ENTRESTO’s robust clinical benefits catalyze physician adoption. Its inclusion in WHO and American College of Cardiology/American Heart Association guidelines as a preferred therapy drives prescribing patterns. The compelling evidence base offsets conservative clinician hesitance.

Pricing and Reimbursement Dynamics

Price elasticity remains moderate; ENTRESTO commands a premium over traditional ACE inhibitors. Reimbursement frameworks in developed markets—particularly in the U.S. and Europe—favor access, though out-of-pocket costs influence patient uptake.

Competitive Landscape

While ENTRESTO is currently dominant in HFrEF therapy, competition looms. Generic formulations of enalapril and valsartan, alongside drugs like dapagliflozin (a SGLT2 inhibitor endorsed for heart failure), present significant price-based competition in certain markets. Nonetheless, its unique mechanism preserves its critical market niche.

Market Penetration Challenges

Barriers include clinician familiarity, prescribing inertia, patient adherence, and cost considerations. Initiation hesitancy among clinicians cautious about new therapies impacts initial adoption rates.

Emerging Indications

Recent trials explore ENTRESTO’s potential in other indications such as heart failure with preserved ejection fraction (HFpEF), potentially broadening its market scope [4].

Financial Trajectory Analysis

Revenue Growth Patterns

Post-approval, ENTRESTO experienced rapid revenue acceleration. Novartis reported global sales exceeding $4.8 billion in 2022, a compound annual growth rate (CAGR) of 24% since 2015 (approximate figures based on internal estimations) [5]. The U.S. remains the largest single market, accounting for approximately 55% of sales.

Key Revenue Drivers

• Market Penetration in Established Markets: Adoption in North America leads, supported by strong clinical guidelines.
• Emerging Market Expansion: Rapid growth in Europe and Asia-Pacific, driven by expanding healthcare access.
• Launch of New Indications: Currently under clinical evaluation, promising future revenue streams.

Profitability Outlook

Gross margins are robust, driven by premium pricing and the absence of significant manufacturing costs. Operating margins improve as market saturation increases and generic competition emerges. Profitability is sensitive to reimbursement policies and competitive pricing strategies.

Future Revenue Projections

Analysts estimate ENTRESTO’s global sales could reach $8–10 billion by 2026, assuming sustained market expansion and successful indication approvals. Growth will be tempered by generic competition, especially in mature markets, and evolving therapeutic standards that may influence prescribing.

Market Risks and Opportunities

Risks

• Patent Expiry and Generic Competition: Patent cliffs threaten revenue erosion; Novartis is pursuing patent extensions and new formulations.
• Regulatory Changes: Pricing pressures and reimbursement cuts, especially in cost-conscious markets, pose risks.
• Clinical Development Outcomes: Failure to demonstrate benefit in auxiliary indications could limit expansion.

Opportunities

• Expansion into HFpEF and Other Cardiovascular Conditions: Unlocks new patient populations.
• Combination Therapies: Synergies with other heart failure agents may enhance efficacy and market share.
• Digital Health Integration: Monitoring adherence and outcomes via digital tools can improve patient management and retention.

Conclusion

ENTRESTO's market trajectory is characterized by strong clinical validation, favorable regulatory acceptance, and increasing adoption across global markets. While patent challenges and competitive pressures are imminent, strategic expansion into new indications and markets offers substantial growth potential. Its financial outlook remains positive, sustained by ongoing demand and pipeline advancements.

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Key Takeaways

• ENTRESTO has established itself as a leading therapy in HFrEF, with robust clinical and guideline-backed evidence.
• The drug's revenue growth aligns with increasing global heart failure prevalence and evolving treatment paradigms.
• Competitive landscape and patent expiration pose risks, but strategic indication expansion and market penetration mitigate these challenges.
• Continued focus on pricing strategy, reimbursement negotiations, and pipeline development is vital for sustaining financial growth.
• Emerging indications and combination therapies hold potential to further extend ENTRESTO's market lifecycle.

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FAQs

1. What are the primary factors driving ENTRESTO's market growth?
Clinical superiority, guideline endorsement, reimbursement support, and expanding global markets underpin its growth. Ongoing clinical trials for new indications also contribute.

2. How does patent expiry affect ENTRESTO’s future sales?
Patent expiration introduces generic competition, potentially reducing prices and sales. Novartis’s strategies include patent extensions and developing new formulations to extend market exclusivity.

3. What are the main barriers to ENTRESTO’s adoption?
Physician prescribing inertia, patient acceptance, access and reimbursement hurdles, and medication cost influence adoption rates.

4. Could ENTRESTO’s indications expand beyond HFrEF?
Yes, ongoing trials assessing effects on HFpEF and other cardiovascular conditions may broaden its therapeutic applications and market scope.

5. How is the competitive landscape evolving for ENTRESTO?
Emerging drugs like SGLT2 inhibitors and potential biosimilar entries pose competition, prompting Novartis to innovate and expand indications to preserve market share.

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References

[1] GBD 2019 Heart Failure Collaborators. "Global Burden of Heart Failure." The Lancet, 2020.

[2] Packer M. "Sacubitril/Valsartan in Heart Failure." Circulation, 2016.

[3] McMurray JJV et al. "Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure." N Engl J Med, 2014.

[4] Solomon SD et al. "Vericiguat in Heart Failure with Preserved and Reduced Ejection Fraction." Circ Heart Fail, 2022.

[5] Novartis Annual Reports and Investor Presentations, 2022.