ENTRESTO SPRINKLE Drug Patent Profile

When do Entresto Sprinkle patents expire, and when can generic versions of Entresto Sprinkle launch?

Entresto Sprinkle is a drug marketed by Novartis and is included in one NDA. There are four patents protecting this drug.

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

The generic ingredient in ENTRESTO SPRINKLE 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 Sprinkle

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

Summary for ENTRESTO SPRINKLE

International Patents:	128
US Patents:	4
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for ENTRESTO SPRINKLE
DailyMed Link:	ENTRESTO SPRINKLE at DailyMed

Pharmacology for ENTRESTO SPRINKLE

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

US Patents and Regulatory Information for ENTRESTO SPRINKLE

ENTRESTO SPRINKLE is protected by four 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	218591-001	Apr 12, 2024		RX	Yes	No	10,722,471		Y
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024		RX	Yes	No	8,877,938		Y	Y
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024		RX	Yes	No	9,388,134
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024		RX	Yes	No	8,101,659		Y
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

Expired US Patents for ENTRESTO SPRINKLE

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-002	Apr 12, 2024	8,101,659
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024	8,101,659

EU/EMA Drug Approvals for ENTRESTO SPRINKLE

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 SPRINKLE

When does loss-of-exclusivity occur for ENTRESTO SPRINKLE?

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

Argentina

Australia

Brazil

Canada

China

Croatia

Cyprus

Denmark

Ecuador

European Patent Office

France

Guatemala

Hong Kong

Hungary

Israel

Japan

Jordan

Lithuania

Malaysia

Mexico

Morocco

New Zealand

Norway

Peru

Poland

Portugal

Russian Federation

Singapore

Slovenia

South Africa

South Korea

Spain

Taiwan

Tunisia

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 SPRINKLE around the world.

Country	Patent Number	Title	Estimated Expiration
Argentina	106613	[HEMI-PENTAHIDRATO DE [3-((1S,3R)-1-BIFENIL-4-ILMETIL-3-ETOXI-CARBONIL-1-BUTIL-CARBAMOIL)-PROPIONATO-(S)-3 -METIL-2 -(PENTANOIL-{2 -(TETRAZOL-5-ILATO)-BIFENIL-4 -ILMETIL}-AMINO)-BUTIRATO] DE TRISODIO
Argentina	057882	COMPUESTOS DE ACCION DOBLE DE BLOQUEADORES DEL RECEPTOR DE ANGIOTENSINA E INHIBIDORES DE ENDOPEPTIDASA NEUTRA
Japan	2005514441
Norway	20073396
Slovenia	2340828
South Korea	20130116381	PHARMACEUTICAL COMBINATIONS OF AN ANGIOTENSIN RECEPTOR ANTAGONIST AND AN NEP INHIBITOR

Supplementary Protection Certificates for ENTRESTO SPRINKLE

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
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
1948158	132016000051118	Italy		PRODUCT NAME: SACUBITRIL/VALSARTAN, COME SACUBITRIL VALSARTAN COMPLESSO DI SALE SODICO (TRISODIO (3-((1S,3R)-1-BIFENIL-4-ILMETIL-3-ETOSSICARBONIL-1-BUTILCARBAMMOIL)PROPIONATO-(S)-3'-METIL-2'-(PENTANOIL(2"-(TETRAZOL-5-ILATO)BIFENIL-4'-ILMETIL)AMMINO)BUTIRRATO) EMIPENTAIDRATO)(ENTRESTO); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/15/1058, 20151123
1948158	16C0018	France		PRODUCT NAME: SACUBITRIL/VALSARTAN,SOUS FORME DE COMPLEXE SODIQUE SACUBITRIL VALSARTAN,C'EST-A-DIRE DE (3-((1S,3R)-1-BIPHENYL-4-YLMETHYL-3-ETHOXYCARBONYL-1-BUTYLCARBAMOYL) PROPIONATE-(S)-3'-METHYL-2'-(PENTANOY(2''-(TETRAZOL-5-YLATE)BIPHENYL-4'-YLMETHYL)AMINO)BUTYRATE)DE TRISODIUM HEMIPENTAHYDRATE; REGISTRATION NO/DATE: EU/1/15/1058 20151123
2340828	301088	Netherlands		PRODUCT NAME: SACUBITRIL/VALSARTAN, ALS SACUBITRIL VALSARTAN NATRIUMZOUTCOMPLEX, DAT WIL ZEGGEN (((S)-N-VALERYL-N-((2'-(1H-TETRAZOL-5-YL)-BIFENYL-4-YL)-METHYL)-VALINE) ((2R,4S)-5-BIFENYL-4-YL-4-(3-CARBOXYPROPIONYLAMINO)-2-METHYL-PENTAANZUURETHYLESTER))NA3-X H2O, WAARBIJ X 0 TOT EN MET 3 IS; REGISTRATION NO/DATE: EU/1/15/1058 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
2340828	LUC00195	Luxembourg		PRODUCT NAME: SACUBITRIL ET VALSARTAN, SOUS FORME DE COMPLEXE DE SEL DE SODIUM SACUBITRIL VALSARTAN, C'EST-A-DIRE (((S)-N-VALERYL-N-((2'-(1H-TETRAZOLE-5-YL)-BIPHENYL-4-YL)-METHYL)-VALINE) ((2R,4S)-5-BIPHENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-ESTER ETHYLIQUE D'ACIDE PENTANOIQUE))NA3 X H2O, DANS LEQUEL X EST 0 A 3; AUTHORISATION NUMBER AND DATE: EU/1/15/1058 20151123

Market Dynamics and Financial Trajectory for Entresto

Introduction

Entresto, a heart-failure drug developed by Novartis, has been a significant focus for the pharmaceutical giant since its approval in July 2015. Despite initial expectations of blockbuster status, the drug's launch has been marked by several challenges. Here, we delve into the market dynamics and financial trajectory of Entresto, highlighting the key factors influencing its performance.

Approval and Initial Launch

Entresto, a combination of sacubitril and valsartan, was approved by the FDA in July 2015 for the treatment of adult patients with symptomatic chronic heart failure with reduced ejection fraction. The initial launch, however, was met with sluggish sales due to several barriers[4].

Barriers to Adoption

Prior Authorization and Payer Hurdles

One of the primary reasons for the slow uptake of Entresto was the high rate of prior authorization requirements. In many cases, physicians had to request prior authorization for patients to access the drug, significantly limiting its adoption. This was particularly evident in the U.S., where patient access was restricted compared to other regions like Switzerland, where access was unrestricted[4].

Physician Reluctance

Physicians were also reluctant to switch patients from existing medications to Entresto, further hindering its sales growth. This reluctance was partly due to the lack of familiarity with the new drug and the perceived risks associated with switching treatments[1].

Marketing and Investment Strategies

To address the slow sales, Novartis significantly increased its marketing investment in Entresto. In 2016, the company announced a $200 million boost in marketing spending to support the U.S. field force, primary care buildout, and additional medical support. This decision was driven by new clinical guidelines from the American College of Cardiology and the American Heart Association, which recommended Entresto as the standard of care for certain heart-failure patients[1].

Unbranded Campaigns

Novartis also launched an unbranded campaign called "Understanding Heart Failure" to raise awareness about heart failure and the benefits of Entresto. This campaign aimed to educate both patients and healthcare providers about the condition and the treatment options available[4].

Financial Performance

Initial Sales Figures

In the first year after its launch, Entresto generated $21 million in sales, with a slow growth rate of $5 million in the fourth quarter of 2015. By the second quarter of 2016, sales had increased to $32 million, still short of the projected $200 million for the year[1][4].

Acceleration in Sales

Despite the initial slow start, Entresto's sales began to accelerate. By the first quarter of 2017, sales had reached $84 million, a significant increase from the previous year. This acceleration was attributed to improved access due to negotiations with payers and favorable treatment guideline recommendations[3].

Projected Revenue

Jefferies analyst Jeffrey Holford predicted that Entresto would hit revenues of $4.7 billion by 2021, surpassing consensus estimates of $3.1 billion. This optimistic outlook was based on the expectation that payer hurdles would continue to fall and enthusiasm among cardiologists would build[3].

Impact of Clinical Guidelines and Payer Access

Clinical Guidelines

The release of new clinical guidelines by major medical societies in May 2016 significantly boosted Entresto's prospects. These guidelines recommended Entresto as the standard of care for certain heart-failure patients, which helped in increasing its adoption among healthcare providers[1].

Payer Access Improvements

Novartis's efforts to negotiate with payers led to improved access for patients. By January 2016, 44% of Medicare patients and 57% of commercial insurance patients had access to Entresto, with a significant portion having lower co-pays. This improvement in access was a crucial factor in the drug's sales acceleration[4].

Pricing and Affordability

Cost to Patients

Entresto is a costly medication, with a cash price of around $730 per month for 60 tablets. However, with insurance coverage, the cost can be significantly reduced. For example, patients with Medicare Part D typically pay less than $50 per month, and those with commercial insurance may pay as little as $10 for a 90-day supply using a copay card[5].

Manufacturer Support

Novartis offers various programs to help patients afford Entresto, including a 30-day free trial and a cost calculator tool on their website. These initiatives aim to make the drug more accessible to those who need it[5].

Regional Performance

U.S. Market

The U.S. market has been a significant focus for Entresto, but it has faced more hurdles compared to other regions. Despite these challenges, the U.S. has seen a gradual improvement in sales, with two-thirds of Entresto's sales coming from this market[3].

European Market

In contrast, Entresto has experienced fewer hurdles in Europe. The drug's initial uptake in Switzerland was five times that of the U.S., largely due to unrestricted access[4].

Analyst Sentiment and Market Impact

Analyst Concerns

Analysts have expressed concerns over the slow uptake of Entresto, which has impacted Novartis's overall financial performance. Sanford Bernstein analyst Tim Anderson noted that the chronic underperformance of Entresto, along with other issues, had damaged investor sentiment[1].

Future Outlook

Despite the initial challenges, analysts like Jeffrey Holford from Jefferies are optimistic about Entresto's future. The expectation is that as payer hurdles continue to fall and clinical guidelines support its use, Entresto will see sustained growth and become a significant contributor to Novartis's revenue[3].

Key Takeaways

• Initial Challenges: Entresto faced slow sales due to prior authorization hurdles and physician reluctance.
• Increased Marketing: Novartis boosted marketing spending by $200 million to support the drug's adoption.
• Clinical Guidelines: Favorable clinical guidelines have significantly improved Entresto's prospects.
• Payer Access: Negotiations with payers have led to improved access for patients.
• Financial Performance: Sales have accelerated, with projected revenues of $4.7 billion by 2021.
• Pricing and Affordability: Various programs are in place to make Entresto more affordable for patients.
• Regional Performance: The U.S. market has seen gradual improvement, while Europe has experienced fewer hurdles.

FAQs

What were the main reasons for the slow adoption of Entresto?

The main reasons for the slow adoption of Entresto included high rates of prior authorization and physicians' reluctance to switch patients from other medications[1].

How did Novartis address the slow sales of Entresto?

Novartis increased its marketing investment by $200 million and launched unbranded campaigns to raise awareness about heart failure and the benefits of Entresto[1][4].

What impact did clinical guidelines have on Entresto's sales?

The release of new clinical guidelines recommending Entresto as the standard of care for certain heart-failure patients significantly boosted its adoption and sales[1].

How has payer access improved for Entresto?

Novartis's negotiations with payers have led to improved access, with a higher percentage of Medicare and commercial insurance patients now having access to the drug with lower co-pays[4].

What is the projected revenue for Entresto by 2021?

Jefferies analyst Jeffrey Holford predicts that Entresto will hit revenues of $4.7 billion by 2021, surpassing consensus estimates[3].

How can patients afford Entresto given its high cost?

Novartis offers various programs, including a 30-day free trial and a cost calculator tool, to help patients afford Entresto. Additionally, insurance coverage can significantly reduce the cost for patients[5].

Sources

1. MMM Online: Novartis ups marketing investment in Entresto, by $200 million.
2. The Toro Company: Form 10-K.
3. BioPharma Dive: Novartis set to ride Entresto wave, says report.
4. MMM Online: Novartis says slow Entresto sales due to limited access.
5. Drugs.com: How much does Entresto cost per month?