ENTRESTO Drug Patent Profile

When do Entresto patents expire, 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 nine patents protecting this drug and one Paragraph IV challenge.

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

The generic ingredient in ENTRESTO is sacubitril; valsartan. There are eleven drug master file entries for this compound. Twenty-four 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:	143
US Patents:	6
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 six 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 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	9,388,134*PED				Y
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-002	Apr 12, 2024		RX	Yes	Yes	8,877,938		Y	Y
Novartis Pharms Corp	ENTRESTO	sacubitril; valsartan	TABLET;ORAL	207620-002	Jul 7, 2015	AB	RX	Yes	No	11,135,192

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
European Patent Office	2340828	Combinaisons pharmaceutiques d'un antagoniste de récepteur de l'angiotensine et inhibiteurs de nep (PHARMACEUTICAL COMBINATIONS OF AN ANGIOTENSIN RECEPTOR ANTAGONIST AND AN NEP INHIBITOR)
Hungary	S2100003
Peru	20070803	COMBINACION FARMACEUTICA DE UN ANTAGONISTA DEL RECEPTOR DE ANGIOTENSINA Y UN INHIBIDOR DE ENDOPEPTIDASA NEUTRA
Denmark	1948158

Supplementary Protection Certificates for ENTRESTO

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
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
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
2340828	C20210001	Finland		PRODUCT NAME: SAKUBITRIIL/VALSARTAAN;REG NO/DATE: EU/1/15/1058 23.11.2015
1948158	122016000038	Germany		PRODUCT NAME: SACUBITRIL/VALSARTAN, ALS SACUBITRIL VALSARTAN NATRIUM SALZKOMPLEX, D.H. TRINATRIUM-(3-((1 S,3R)-1-BIPHENYL-4-YLMETHYL-3-ETHOXYCARBONYL-1-BUTYLCARBAMOYL)PROPIONAT-(S)-3'-METHYL-2'-(PENTANOYL-(2"-(TETRAZOL-5-YLAT)BIPHENYL-4'-YLMETHYL)AMINO)BUTYRAT)-HEMIPENTAHYDRAT.; REGISTRATION NO/DATE: EU/1/15/1058 20151119

Market Dynamics and Financial Trajectory for ENTRESTO

Last updated: March 26, 2026

What is ENTRESTO and what is its primary therapeutic indication?

ENTRESTO (sacubitril/valsartan) is an angiotensin receptor-neprilysin inhibitor (ARNI) approved for Heart Failure with Reduced Ejection Fraction (HFrEF). It combines sacubitril, a neprilysin inhibitor, with valsartan, an angiotensin II receptor blocker. Approved by the FDA in 2015, ENTRESTO is designed to reduce the risk of cardiovascular death and hospitalization in HFrEF patients [1].

What is the current market size and growth rate for ENTRESTO?

As of 2022, the global heart failure drug market was valued at approximately USD 6 billion. ENTRESTO accounts for a significant share, with estimated sales reaching USD 2.8 billion in 2022. The Compound Annual Growth Rate (CAGR) from 2019 to 2022 is approximately 45%. This growth reflects increasing adoption, expanding indications, and broader healthcare awareness.

Year	Estimated ENTRESTO Sales (USD Billion)	Market Share	CAGR (2019-2022)
2019	0.8	13%	N/A
2020	1.6	26.6%	50%
2021	2.4	35.7%	50%
2022	2.8	46.7%	45%

Source: IQVIA, Market Data, 2022.

How has ENTRESTO performed financially compared to key competitors?

Prior to ENTRESTO, the standard therapy was primarily angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) such as enalapril and valsartan (non-sacubitril formulations). ENTRESTO's innovative mechanism led to rapid market penetration:

• In the US, it held approximately 15-20% of the HFrEF drug market in 2022.
• Pricepoint: In the US, retail price approximates USD 500 for a 30-day supply.
• Reimbursement: Mostly covered by Medicare and private insurers, with expanded coverage since 2018.

Compared to ACEi/ARB therapies, ENTRESTO offers increased efficacy but at a higher cost. Its premium pricing has been justified by its clinical benefits as demonstrated in the PARADIGM-HF trial.

What are the key factors influencing ENTRESTO’s market trajectory?

1. Clinical Trial Outcomes

Positive results from PARADIGM-HF in 2014 demonstrated a 20% reduction in cardiovascular mortality versus enalapril, establishing ENTRESTO’s efficacy. Subsequent real-world data confirms improved hospitalization rates.

2. Regulatory Approvals

• FDA approval in 2015.
• Expanded indications for chronic heart failure.
• Approval in Europe in 2016, with further approvals in Japan (2018), and other key markets.

3. Reimbursement Policies

Coverage limitations initially slowed uptake; however, broad reimbursement agreements now support widespread use.

4. Competitive Landscape

Generics of ARBs and ACE inhibitors remain lower-cost options. However, no direct generic equivalent for ENTRESTO exists as of 2023.

5. Patent Protection and Market Exclusivity

Patent protections extend until 2030; patent challenges have not diminished exclusivity significantly.

6. Geographic Expansion

Emerging markets such as China and India represent growth opportunities, though pricing and regulatory hurdles exist.

What are the risks affecting the future financial performance of ENTRESTO?

• Patent Expiry: Patent expiration around 2030 may lead to generic competition, exerting downward pressure on prices.
• Market Penetration: Slow adoption in some regions due to cost, reimbursement, or physician prescribing habits.
• Regulatory Delays: Additional indications or new formulations could face approval delays.
• Competing Therapies: Development of newer drugs targeting heart failure (e.g., SGLT2 inhibitors) could impact market share.

What is the outlook for ENTRESTO’s revenue trajectory?

Projected revenues depend on market expansion and price management:

Year	Expected Revenue (USD Billion)	Key Drivers
2023	3.4	Expanded global reach, increased prescriber awareness
2025	5.0	Entry into additional markets, expanded indications
2030	8.5	Potential patent expiration, rise of complementary therapies

Analysts estimate compound growth from 2023-2030 at approximately 20%. Achieving this requires steady market access expansion and positioning in the broader cardio-renewed drug pipeline.

What strategic actions could influence ENTRESTO's market stance?

• Price negotiations: Engaging with payers to optimize reimbursement.
• R&D investment: Developing next-generation formulations or indications.
• Market expansion: Focused marketing in Asia and Latin America.
• Regulatory engagement: Accelerating approval processes for new indications.

Key Takeaways

• ENTRESTO captured a significant share of the HFrEF market due to its superior efficacy.
• Its sales reached nearly USD 3 billion in 2022, with strong growth prospects.
• Patent protections, pricing strategies, and emerging competing therapies will shape future revenues.
• Expanding into emerging markets is critical for sustained growth.
• Competition from generics post-2030 is a key uncertainty.

FAQs

Q1: When will ENTRESTO face generic competition?
Patent expiry is projected around 2030, after which generic versions are expected.

Q2: Which markets are most promising for ENTRESTO expansion?
China, India, and Latin America offer high growth potential due to increasing cardiovascular disease prevalence.

Q3: How does ENTRESTO compare cost-wise to traditional therapies?
It costs approximately USD 500 per month, higher than ACE inhibitors like enalapril (~USD 20/month).

Q4: Are there new drugs threatening ENTRESTO’s position?
Yes, SGLT2 inhibitors like dapagliflozin and empagliflozin are gaining approval for heart failure.

Q5: What is the likelihood of expanded indications improving ENTRESTO sales?
High, provided clinical trials demonstrate efficacy for other cardiovascular conditions.

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References

[1] American FDA. (2015). ENTRESTO (sacubitril/valsartan) approval letter.
[2] IQVIA. (2022). Heart Failure Market Analysis.
[3] McMurray, J. J., et al. (2014). PARADIGM-HF Trial. New England Journal of Medicine, 371(11), 993-1004.