Sacubitril; valsartan - Generic Drug Details

What are the generic sources for sacubitril; valsartan and what is the scope of freedom to operate?

Sacubitril; valsartan is the generic ingredient in three branded drugs marketed by Novartis, Novartis Pharms Corp, Alembic, Alkem Labs Ltd, Biocon Pharma, Crystal, Dr Reddys, Laurus, Lupin, Macleods Pharms Ltd, MSN, Torrent, and Zydus Pharms, and is included in thirteen NDAs. There are eleven patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Sacubitril; valsartan has one hundred and eighty-two patent family members in forty-four countries.

Nine suppliers are listed for this compound.

Summary for sacubitril; valsartan

International Patents:	182
US Patents:	11
Tradenames:	3
Applicants:	13
NDAs:	13
Finished Product Suppliers / Packagers:	9
Clinical Trials:	91
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for sacubitril; valsartan
DailyMed Link:	sacubitril; valsartan at DailyMed

Recent Clinical Trials for sacubitril; valsartan

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

Sponsor	Phase
Dr. Reddy's Laboratories (Thailand) Limited	Phase 1
Rede de Investigação em Saúde	Phase 4
Universidade do Porto	Phase 4

See all sacubitril; valsartan clinical trials

Pharmacology for sacubitril; valsartan

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

Anatomical Therapeutic Chemical (ATC) Classes for sacubitril; valsartan

C09CA	Angiotensin II receptor blockers (ARBs), plain
C09C	ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), PLAIN
C09	AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
C	Cardiovascular system

Paragraph IV (Patent) Challenges for SACUBITRIL; VALSARTAN

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 sacubitril; valsartan

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Alembic	SACUBITRIL AND VALSARTAN	sacubitril; valsartan	TABLET;ORAL	213682-001	May 28, 2024	AB	RX	No	No
Novartis Pharms Corp	ENTRESTO	sacubitril; valsartan	TABLET;ORAL	207620-003	Jul 7, 2015	AB	RX	Yes	Yes	8,877,938*PED				Y
Macleods Pharms Ltd	SACUBITRIL AND VALSARTAN	sacubitril; valsartan	TABLET;ORAL	213728-003	Oct 16, 2024	AB	RX	No	No
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024		RX	Yes	No	8,101,659		Y
Crystal	SACUBITRIL AND VALSARTAN	sacubitril; valsartan	TABLET;ORAL	213605-003	May 28, 2024	AB	RX	No	No
Novartis Pharms Corp	ENTRESTO	sacubitril; valsartan	TABLET;ORAL	207620-001	Jul 7, 2015	AB	RX	Yes	No	8,101,659*PED				Y

Expired US Patents for sacubitril; valsartan

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

EU/EMA Drug Approvals for sacubitril; valsartan

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
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
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

International Patents for sacubitril; valsartan

Country	Patent Number	Title	Estimated Expiration
Netherlands	300811
Tunisia	2015000028	NEP INHIBITORS FOR TREATING DISEASES CHARACTERIZED BY ATRIAL ENLARGEMENT OR REMODELING
Spain	2945866
Norway	20043380
European Patent Office	3294283	SCHÉMA POSOLOGIQUE DU SACUBITRIL-VALSARTAN POUR LE TRAITEMENT DE L'INSUFFISANCE CARDIAQUE (SACUBITRIL-VALSARTAN DOSAGE REGIMEN FOR TREATING HEART FAILURE)
Hungary	E050870

Supplementary Protection Certificates for sacubitril; valsartan

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1948158	2016C/026	Belgium		PRODUCT NAME: SACUBITRIL/VALSARTAN, ALS SACUBITRIL VALSARTAN NATRIUMZOUT COMPLEX, I.E. TRINATRIUM (3-((1S,3R)-1-BIFENYL-4-YLMETHYL-3-ETHOXYCARBONIL-1-BUTYLCARBAMOYL)PROPIONAAT-(S)-3'-METHYL-2'-(PENTANOYL(2-(TETRAZOL-5-YLATE)BIFENYL-4'-YLMETHYL)AMINO)BUTYRAAT)HEMIPENTAHYDRAAT; AUTHORISATION NUMBER AND DATE: EU/1/15/1058 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
1467728	300811	Netherlands		PRODUCT NAME: SACUBITRIL/VALSARTAN, MET INBEGRIP VAN FARMACEUTISCH AANVAARDBARE ZOUTEN DAARVAN; REGISTRATION NO/DATE: EU/1/15/1058 (C(2015) 8288) 20151123
1467728	C01467728/01	Switzerland		PRODUCT NAME: SACUBRITIL UND VALSARTAN; REGISTRATION NO/DATE: SWISSMEDIC-ZULASSUNG 65673 17.09.2015
2340828	CA 2021 00001	Denmark		PRODUCT NAME: SACUBITRIL/VALSARTAN, SOM SACUBITRILVALSARTAN-NATRIUMSALTKOMPLEKS, DVS. ...; REG. NO/DATE: EU/1/15/1058 20151123
1467728	16C0019	France		PRODUCT NAME: SACUBITRIL/VALSARTAN,Y COMPRIS LEURS SELS PHARMACEUTIQUEMENT ACCEPTABLES; REGISTRATION NO/DATE: EU/1/15/1058 20151123

Market Dynamics and Financial Trajectory for Sacubitril/Valsartan

Introduction

Sacubitril/valsartan, marketed under the brand name Entresto, is a groundbreaking medication for the treatment of heart failure with reduced ejection fraction (HFrEF). Since its approval, the drug has navigated a complex market landscape, influenced by various factors including clinical efficacy, economic viability, and regulatory environments.

Clinical Efficacy and Economic Value

The clinical efficacy of sacubitril/valsartan has been well-documented, particularly in reducing mortality and hospitalization rates in patients with HFrEF. Economic evaluations have shown that the drug provides high economic value, especially for patients with ejection fractions (EF) of 50% or less. Studies indicate that sacubitril/valsartan increases quality-adjusted life-years (QALYs) at an incremental cost-effectiveness ratio (ICER) consistent with high economic value[1][2].

Cost-Effectiveness Analysis

Cost-effectiveness analyses using data from the PARADIGM-HF and PARAGON-HF trials have demonstrated that sacubitril/valsartan offers significant health benefits at a reasonable cost. For patients with EF ≤50%, the ICER is below $60,000 per QALY, indicating high economic value. For those with EF ≤60%, the ICER is below $180,000 per QALY, suggesting intermediate economic value[2].

Market Adoption and Prescription Patterns

Despite its clinical and economic benefits, the initial market adoption of sacubitril/valsartan was slow. However, over the past few years, there has been a significant increase in prescriptions. A study using IQVIA Inc. National Prescription Audit™ data showed a 5.6-fold increase in sacubitril/valsartan prescriptions from 2016 to 2019, totaling 3.3 million prescriptions. This growth indicates increasing acceptance among healthcare providers and patients[5].

Prescription Strength and Demographics

The majority of prescriptions are for the lower strength (24/26 mg), with only about 20.6% at the target strength (97/103 mg). Younger patients are more likely to be prescribed the target strength compared to older patients. Cardiologists are the primary prescribers, accounting for 59% of all dispensed prescriptions, although non-cardiologists have shown a greater increase in prescribing the drug over time[5].

Financial Performance and Market Traction

After a slow start, Novartis, the manufacturer of Entresto, has seen significant financial gains. In 2017, sales of Entresto skyrocketed 244% year-over-year to $110 million, exceeding analyst expectations. This growth was partly due to reduced prior authorization requirements and negotiated pay-for-performance deals with insurance companies[3].

Revenue and Sales Projections

While Entresto has not yet reached the peak sales of $6 billion initially projected, it is on a positive trajectory. Novartis reported that the drug was on track to reach sales of $500 million in 2017, and subsequent years have seen continued growth. The company's stock has risen in response to these positive financial indicators[3].

Reimbursement and Access

Access to sacubitril/valsartan has been a critical factor in its market success. Initially, high costs and prior authorization requirements were significant barriers. However, Novartis's efforts to negotiate with insurance companies and implement pay-for-performance deals have improved access. For example, the copay for more than half of Medicare patients is now less than $10, making the drug more affordable[3].

Regulatory and Clinical Trials

Novartis has continued to invest in clinical trials and data collection to support the benefits of sacubitril/valsartan. The FortiHFy clinical program includes over 40 studies, some of which are focused on pediatric patients and the drug's ability to improve exercise capacity in adults with heart failure. These studies help build a robust evidence base and support reimbursement negotiations[3].

Industry and Market Trends

The heart failure treatment market is highly competitive, with generic drugs dominating the landscape. However, sacubitril/valsartan's unique mechanism of action and proven clinical benefits have allowed it to carve out a significant market share. The drug's success has also prompted discussions about outcomes-based reimbursement models, which could further enhance its market position[3].

Barriers to Use and Future Directions

Despite the growth in prescriptions, there are still barriers to the widespread adoption of sacubitril/valsartan. These include the need for dosing uptitration and the clinical implications of underutilization. Further research is needed to address these issues and ensure that all eligible patients receive the treatment[5].

Industry Marketing and Physician Influence

Industry marketing efforts, including payments to physicians, have played a role in increasing prescription rates. A study found that nearly 28% of eligible physician prescribers received at least one meal payment related to sacubitril/valsartan, highlighting the influence of industry marketing on prescription patterns[4].

Key Takeaways

• Clinical Efficacy: Sacubitril/valsartan has proven clinical benefits in reducing mortality and hospitalization rates in patients with HFrEF.
• Economic Value: The drug offers high economic value for patients with EF ≤50% and intermediate economic value for those with EF ≤60%.
• Market Adoption: Despite initial slow adoption, prescriptions have increased significantly over the past few years.
• Financial Performance: Novartis has seen substantial financial gains from Entresto sales, with continued growth projected.
• Reimbursement and Access: Negotiated pay-for-performance deals and reduced prior authorization requirements have improved access to the drug.
• Clinical Trials and Evidence: Ongoing clinical trials and data collection support the drug's benefits and reimbursement negotiations.

FAQs

What is the clinical efficacy of sacubitril/valsartan in treating heart failure?

Sacubitril/valsartan has been shown to reduce mortality and hospitalization rates in patients with heart failure with reduced ejection fraction (HFrEF), providing significant clinical benefits.

How cost-effective is sacubitril/valsartan compared to other treatments?

Sacubitril/valsartan offers high economic value for patients with EF ≤50% and intermediate economic value for those with EF ≤60%, with an ICER below $60,000 and $180,000 per QALY, respectively.

What factors have contributed to the increased market traction of sacubitril/valsartan?

Reduced prior authorization requirements, negotiated pay-for-performance deals, and industry marketing efforts have all contributed to the increased market traction of sacubitril/valsartan.

How has the financial performance of sacubitril/valsartan evolved since its launch?

After a slow start, sacubitril/valsartan has seen significant financial gains, with sales increasing by 244% year-over-year in 2017 and continued growth thereafter.

What are the main barriers to the widespread adoption of sacubitril/valsartan?

Barriers include the need for dosing uptitration, clinical implications of underutilization, and high costs, although these are being addressed through various strategies.

How does sacubitril/valsartan fit into the broader heart failure treatment market?

Sacubitril/valsartan has carved out a significant market share due to its unique mechanism of action and proven clinical benefits, despite competition from generic drugs.

Sources

1. Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure. JAMA Cardiology, 2023.
2. Economic Evaluation of Sacubitril/Valsartan for HF. American College of Cardiology, 2023.
3. After a slow start, Novartis finally gains market traction with heart drug Entresto. FiercePharma, 2017.
4. Industry marketing payments to physicians and prescription patterns. Heart, 2024.
5. National Trends in the Use of Sacubitril/Valsartan. PubMed, 2021.

Last updated: 2024-12-16