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 twelve patents protecting this drug and one Paragraph IV challenge.

This drug has one hundred and sixty-three 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. Nine 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:	163
US Patents:	8
Applicants:	2
NDAs:	2
Finished Product Suppliers / Packagers:	2
Raw Ingredient (Bulk) Api Vendors:	13
Clinical Trials:	41
Patent Applications:	22
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
Dr. Reddy's Laboratories (Thailand) Limited	Phase 1
Boehringer Ingelheim laboratory	Phase 2/Phase 3
Instituto Nacional de Cardiologia Ignacio Chavez	Phase 2/Phase 3

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 eight US patents and one FDA Regulatory Exclusivity.

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
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024		RX	Yes	No			Y
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024		RX	Yes	No
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-002	Apr 12, 2024		RX	Yes	Yes			Y
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-002	Apr 12, 2024		RX	Yes	Yes

EU/EMA Drug Approvals for ENTRESTO

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Novartis Europharm Limited	Entresto	sacubitril, valsartan	EMEA/H/C/004062 Paediatric 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
Novartis Europharm Limited	Neparvis	sacubitril, valsartan	EMEA/H/C/004343 Paediatric 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

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
Australia	2003206738
China	108685889
Poland	1948158
Spain	2879550
Spain	2449765

Supplementary Protection Certificates for ENTRESTO

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2340828	2/2021	Austria		PRODUCT NAME: SACUBITRIL/VALSARTAN ALS SACUBITRIL-VALSARTAN-NATRIUMSALZ-KOMPLEX, D.H. (((S)-N-VALERYL-N-((2'-(1H-TETRAZOL-5-YL)BIPHENYL-4-YL)METHYL)-VALIN) ((2R,4S)-5-BIPHENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-PENTANSAEUREETHYLESTER))NA3 ? X H2O, WOBEI X FUER 0 BIS 3 STEHT; REGISTRATION NO/DATE: EU/1/15/1058 (MITTEILUNG) 20151123
1467728	93074	Luxembourg		PRODUCT NAME: SACUBITRIL/VALSARTAN, Y COMPRIS LES SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELUI-CI; FIRST REGISTRATION DATE: 20151123
1948158	C 2016 017	Romania		PRODUCT NAME: SACUBITRIL/VALSARTAN, SUB FORMA DE COMPLEX DE SARURI DE SODIU; NATIONAL AUTHORISATION NUMBER: EU/1/15/1058/001-016; DATE OF NATIONAL AUTHORISATION: 20151119; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/15/1058/001-016; DATE OF FIRST AUTHORISATION IN EEA: 20151119
1948158	C01948158/01	Switzerland		PRODUCT NAME: SACUBITRIL UND VALSARTAN; REGISTRATION NO/DATE: SWISSMEDIC-ZULASSUNG 65673 17.09.2015
1948158	C20160014 00383	Estonia		PRODUCT NAME: SAKUBITRIIL/VALSARTAAN;REG NO/DATE: EU/1/15/1058 23.11.2015

Market Dynamics and Financial Trajectory for the Drug: Entresto

Introduction

Entresto, a groundbreaking heart failure medication developed by Novartis, has been a significant player in the pharmaceutical market since its approval in 2015. The drug, a combination of sacubitril and valsartan, has shown remarkable growth and has become a cornerstone in Novartis' portfolio. Here, we delve into the market dynamics and financial trajectory of Entresto.

Mechanism of Action and Indications

Entresto works by combining the effects of sacubitril, a neutral endopeptidase inhibitor, and valsartan, an angiotensin receptor blocker. This combination helps in reducing the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure and reduced ejection fraction. It is also indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older, as well as for the treatment of hypertension[1].

Initial Launch and Early Challenges

Despite its potential, Entresto's launch was initially sluggish due to barriers such as limited patient access and underfunded marketing efforts. In 2016, sales totaled only $170 million, significantly below Novartis' forecast of $200 million. However, Novartis invested heavily in the drug and negotiated with payers to improve access, leading to a gradual increase in sales[3].

Acceleration in Sales

By 2017, there was a noticeable acceleration in Entresto's sales. Novartis reported revenue growth of $67 million in the first quarter of 2017 compared to the previous year. Analysts like Jeffrey Holford from Jefferies predicted continued growth, estimating revenues to hit $4.7 billion by 2021, surpassing consensus estimates of $3.1 billion[3].

Recent Sales Performance

In recent years, Entresto has become one of Novartis' top-selling assets. By 2023, global sales of Entresto reached $6.035 billion, with a historical growth rate (CAGR) of 34% between 2020 and 2023. This growth was driven by strong performance across various regions, including the U.S., where two-thirds of the sales were generated[1][4].

Financial Impact on Novartis

Entresto's success has significantly contributed to Novartis' financial performance. In the third quarter of 2024, Novartis reported a 10% increase in net sales, with Entresto contributing a 26% growth in constant currency terms. The drug's strong sales have been a key driver of Novartis' operating income and net income, which saw increases of 39% and 62%, respectively, in 2023 compared to the previous year[2][5].

Market Dynamics and Competition

Despite its success, Entresto faces challenges from generic competition and regulatory pressures. In 2024, an appeals court ruled against Novartis' bid to block the entry of a generic version of Entresto by MSN Pharmaceuticals. Additionally, the Inflation Reduction Act's drug price negotiation program, which includes Entresto, could impact its pricing and sales starting in 2026[4].

Global Reach and Regulatory Approvals

Entresto is sold globally, including in the U.S., the UK, France, Germany, and Japan. Its approval and inclusion in treatment guidelines in these regions have been crucial for its market penetration. The drug's indications have been expanded to include pediatric patients, further broadening its market reach[1].

Analyst Insights and Projections

Analysts continue to be optimistic about Entresto's future. The drug's sales are expected to continue growing, albeit at a slower rate due to impending generic competition. However, Novartis' efforts to negotiate with payers and its ongoing innovation in the cardiovascular therapy area are expected to mitigate some of these challenges[3][4].

Key Statistics

• Global Sales in 2023: $6.035 billion[1]
• Historical CAGR (2020-2023): 34%[1]
• Q3 2024 Sales Growth: 26% in constant currency terms[5]
• Net Sales Contribution to Novartis: Significant contributor to Novartis' $45.4 billion in net sales for 2023[2]
• Generic Competition: Entry of generic versions expected to impact sales starting in 2026[4]

Conclusion

Entresto has transformed from a slow-starting drug to a blockbuster asset for Novartis, driven by its unique mechanism of action, expanded indications, and strategic marketing efforts. Despite facing challenges from generic competition and regulatory pressures, Entresto remains a critical component of Novartis' financial success and a leader in the cardiovascular therapy market.

Key Takeaways

• Entresto is a combination of sacubitril and valsartan, indicated for heart failure and hypertension.
• The drug experienced initial launch challenges but has since shown significant sales growth.
• Entresto has become one of Novartis' top-selling assets, contributing substantially to the company's financial performance.
• The drug faces future challenges from generic competition and regulatory price controls.
• Analysts remain optimistic about its continued growth despite these challenges.

FAQs

What is Entresto and how does it work?

Entresto is a heart failure medication that combines sacubitril, a neutral endopeptidase inhibitor, and valsartan, an angiotensin receptor blocker. It works by reducing the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure and reduced ejection fraction[1].

What were the initial challenges faced by Entresto after its launch?

Entresto faced barriers such as limited patient access and underfunded marketing efforts, leading to slower-than-expected sales growth in its early years[3].

How has Entresto's sales performance evolved over the years?

Entresto's sales have accelerated significantly since its initial launch. By 2023, global sales reached $6.035 billion, with a historical CAGR of 34% between 2020 and 2023[1].

What impact has Entresto had on Novartis' financial performance?

Entresto has been a key driver of Novartis' operating income and net income, contributing to the company's overall financial growth and success[2][5].

What challenges does Entresto face in the future?

Entresto faces challenges from generic competition and the Inflation Reduction Act's drug price negotiation program, which could impact its pricing and sales starting in 2026[4].

How does Entresto's global reach contribute to its market success?

Entresto is sold globally, including in major markets like the U.S., the UK, France, Germany, and Japan. Its approval and inclusion in treatment guidelines in these regions have been crucial for its market penetration[1].

Sources

1. GlobalData, "The Global Drug sales of Entresto (2020 - 2026, USD Millions)"
2. Novartis, "Novartis Financial Results Q4 2023 – English"
3. BioPharma Dive, "Novartis set to ride Entresto wave, says report"
4. BioSpace, "Novartis Loses Appeal to Bar Entresto Generic From U.S. Market"
5. Novartis, "Novartis continues strong momentum in Q3 with 10% sales growth ..."