ZONTIVITY Drug Patent Profile

Which patents cover Zontivity, and when can generic versions of Zontivity launch?

Zontivity is a drug marketed by Key Therap and is included in one NDA. There is one patent protecting this drug.

This drug has one hundred and sixty-four patent family members in thirty-seven countries.

The generic ingredient in ZONTIVITY is vorapaxar sulfate. Additional details are available on the vorapaxar sulfate profile page.

DrugPatentWatch^® Generic Entry Outlook for Zontivity

Zontivity was eligible for patent challenges on May 8, 2018.

By analyzing the patents and regulatory protections it appears that the earliest date for generic entry will be December 23, 2027. This may change due to patent challenges or generic licensing.

Indicators of Generic Entry

Summary for ZONTIVITY

International Patents:	164
US Patents:	1
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	108
Clinical Trials:	5
Patent Applications:	713
Drug Prices:	Drug price information for ZONTIVITY
What excipients (inactive ingredients) are in ZONTIVITY?	ZONTIVITY excipients list
DailyMed Link:	ZONTIVITY at DailyMed

See drug prices for ZONTIVITY

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for ZONTIVITY

Constraining patent/regulatory exclusivity:

7,304,078

NDA:

204886

Dosage:

TABLET;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Recent Clinical Trials for ZONTIVITY

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

Sponsor	Phase
Vanderbilt University Medical Center	Phase 4
Vanderbilt University	Phase 4
University of Florida	Phase 4

See all ZONTIVITY clinical trials

US Patents and Regulatory Information for ZONTIVITY

ZONTIVITY is protected by one US patents.

This potential generic entry date is based on patent 7,304,078.

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

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Key Therap	ZONTIVITY	vorapaxar sulfate	TABLET;ORAL	204886-001	May 8, 2014		DISCN	Yes	No	7,304,078		Y	Y

Expired US Patents for ZONTIVITY

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Key Therap	ZONTIVITY	vorapaxar sulfate	TABLET;ORAL	204886-001	May 8, 2014	7,235,567
Key Therap	ZONTIVITY	vorapaxar sulfate	TABLET;ORAL	204886-001	May 8, 2014	7,713,999

International Patents for ZONTIVITY

See the table below for patents covering ZONTIVITY around the world.

Country	Patent Number	Title	Estimated Expiration
Portugal	1495018
Brazil	PI0309309	antagonistas de receptor de trombina tricíclicos
Russian Federation	2355689	КРИСТАЛЛИЧЕСКАЯ ПОЛИМОРФНАЯ ФОРМА БИСУЛЬФАТНОЙ СОЛИ АНТАГОНИСТА ТРОМБИНОВОГО РЕЦЕПТОРА (CRYSTALLINE POLYMORPHOUS FORM OF THROMBIN RECEPTOR ANTAGONIST BISULFATE)
Brazil	0309309	Antagonistas de receptor de trombina tricìclicos
China	1910176	Crystalline polymorph of a bisulfate salt of a thrombin receptor antagonist
Spain	2291323

Supplementary Protection Certificates for ZONTIVITY

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1495018	34/2015	Austria		PRODUCT NAME: VORAPAXAR, ODER EIN PHARMAZEUTISCH ANNEHMBARES SALZ ODER SOLVAT DAVON; REGISTRATION NO/DATE: EU/1/14/976 20150119
1495018	2015C/037	Belgium		PRODUCT NAME: VORAPAXAR, OU SON SEL OU SOLVAT PHARMACOLOGIQUEMENT ADMISSIBLE; AUTHORISATION NUMBER AND DATE: EU/1/14/976/001
1495018	15C0047	France		PRODUCT NAME: VORAPAXAR,OU L'UN DE SES SELS OU SOLVATES PHARMACEUTIQUEMENT ACCEPTABLES; REGISTRATION NO/DATE: EU/1/14/976/001-006 20150121
1495018	300746	Netherlands		PRODUCT NAME: VORAPAXAR, DESGEWENST IN DE VORM VAN EEN FARMACEUTISCH AANVAARDBAAR ZOUT OF SOLVAAT, IN HET BIJZONDER VORAPAXARSULFAAT; REGISTRATION NO/DATE: EU/1/14/976/001-006 20150121
1495018	C20150025 00159	Estonia		PRODUCT NAME: VORAPAKSAAR;REG NO/DATE: EU/1/14/976 21.01.2015
1495018	2015/035	Ireland		PRODUCT NAME: VORAPAXAR, OR A PHARMACEUTICALLY ACCEPTABLE SALT OR SOLVATE THEREOF; REGISTRATION NO/DATE: EU/1/14/976/001-006 20150119

Market Dynamics and Financial Trajectory for ZONTIVITY

Last updated: July 27, 2025

Introduction

ZONTIVITY (vorapaxar) is an oral protease-activated receptor-1 (PAR-1) antagonist developed by Merck & Co., primarily prescribed for reducing thrombotic cardiovascular events. Since its FDA approval in 2014, ZONTIVITY has encountered complex market dynamics driven by evolving clinical evidence, regulatory considerations, competitive landscape, and shifting cardiology treatment paradigms. This analysis examines these factors and projects the drug’s financial trajectory over the coming years.

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Market Overview and Indications

ZONTIVITY addresses the unmet need for secondary prevention in patients with a history of myocardial infarction (MI), peripheral arterial disease (PAD), or at high risk of recurrent ischemic events. It aims to reduce the incidence of myocardial infarction, stroke, cardiovascular death, and limb ischemia, targeting a niche segment within the broader antithrombotic market.

The drug’s user base predominantly comprises cardiologists and vascular specialists, with its prescribing pattern influenced by combination therapies involving aspirin, P2Y12 inhibitors, and other antiplatelet agents. The total addressable market depends on the prevalence of high-risk cardiovascular conditions and clinicians’ acceptance of ZONTIVITY as part of therapeutic regimens.

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Market Dynamics

Clinical Evidence and Regulatory Landscape

ZONTIVITY's market trajectory is closely tied to the clinical evidence supporting its efficacy and safety profile. The TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction) trial failed to demonstrate a significant benefit in the general population of acute coronary syndrome (ACS) patients, limiting its broader application [1].

Conversely, subsequent studies, such as the TRA 2°P-TIMI 50 trial, indicated a reduction in ischemic events in secondary prevention, particularly in PAD and prior MI populations. However, concerns over increased bleeding risks tempered enthusiasm among clinicians, leading to cautious off-label use.

Regulatory agencies have maintained a focused indication for ZONTIVITY, with some regions endorsing its use in patients with established cardiovascular disease, balancing thrombotic risk reduction against hemorrhagic complications.

Competitive Environment

ZONTIVITY competes within the antithrombotic space, dominated by well-established agents like aspirin, clopidogrel, ticagrelor, and newer anticoagulants such as rivaroxaban and apixaban. Its niche positioning is challenged by these alternatives, which have broader indications and more extensive clinical data.

The limited scope of ZONTIVITY’s indications, combined with safety concerns, restricts widespread adoption, compelling Merck to focus on specific high-risk subpopulations where its benefit-risk profile is favorable.

Physician Adoption and Prescribing Patterns

Adoption hinges on clinicians’ confidence in balancing efficacy against bleeding risks. The drug’s complexity and the need for careful patient selection hinder rapid expansion. Educational initiatives and updated guidelines may influence its adoption curve, potentially improving utilization in targeted populations.

Pricing and Reimbursement

Pricing strategies impact revenue prospects; ZONTIVITY is marketed at a premium, justified by its specialized indication. Reimbursement policies are crucial, especially in cost-sensitive healthcare systems. Favorable formulary positioning and demonstrated cost-effectiveness in selected cohorts could improve market penetration.

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Financial Trajectory and Revenue Projections

Historical Performance

Since its approval, ZONTIVITY’s sales growth has been modest, constrained by limited adoption and off-label use. Merck reported global sales of approximately $30 million in 2021, reflecting slow uptake compared to initial projections [2]. This subdued performance underscores the challenges of commercializing niche cardiovascular agents.

Forecasting Future Revenue

Projections suggest that ZONTIVITY's revenues will remain relatively stable or exhibit slow growth over the next five years unless driven by:

• Expansion into new or underserved territories: Navigating regulatory pathways in emerging markets can unlock additional revenue streams.
• Increased adoption in high-risk cohorts: Improved patient selection, coupled with clinician education, may bolster prescriptions.
• Combination therapy advancements: Demonstrable benefits when used alongside other agents could expand its market.

In a conservative scenario, revenues may remain within the range of $20–50 million annually through 2025, given the current prescribing landscape (see Table 1). Optimistic scenarios, backed by targeted clinical endorsements and strategic marketing, could see annual revenues surpassing $100 million by mid-decade.

Potential Growth Catalysts

• New clinical data: Ongoing or future studies demonstrating clear benefits could enhance clinician confidence.
• Regulatory expansions: Broader approvals for additional indications could significantly elevate sales.
• Strategic partnerships: Collaborations with payers and healthcare providers to promote patient identification can facilitate higher utilization.

Risks and Challenges

• Bleeding risks: As a potent antithrombotic, the bleeding profile remains a barrier, particularly in an aging, polypharmacy-prone population.
• Market hesitancy: Clinician preference for established therapies limits ZONTIVITY’s market share.
• Pricing pressures: Reimbursement constraints could restrict access and profitability.

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Conclusion

ZONTIVITY’s market dynamics are characterized by niche positioning within the broader antithrombotic landscape, constrained by safety concerns and limited indication expansion. While its clinical benefits are recognized in certain high-risk subgroups, practical adoption faces hurdles. Financially, the drug’s trajectory is likely to be slow-growth unless new data, expanded indications, or strategic market initiatives materialize. Merck’s ongoing efforts to delineate its optimal use cases and educate prescribing clinicians will be pivotal in shaping its long-term commercial success.

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Key Takeaways

• Limited Adoption: Despite FDA approval, ZONTIVITY’s niche indication and safety profile restrict widespread use.
• Clinical Evidence Impact: Ongoing interpretations of efficacy versus safety heavily influence market acceptance.
• Competitive Challenges: Major antithrombotic agents' dominance caps ZONTIVITY’s market share.
• Revenue Outlook: Expected to see slow, incremental growth; significant expansion contingent on clinical, regulatory, and market strategies.
• Strategic Focus: Targeted marketing, guideline updates, and potential indication expansion could serve as growth catalysts.

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FAQs

1. What is the primary indication for ZONTIVITY?
ZONTIVITY is approved for reducing thrombotic cardiovascular events in patients with a history of MI or with PAD at risk of recurrent events, emphasizing secondary prevention.

2. How does ZONTIVITY compare to other antithrombotic agents?
Compared to aspirin and P2Y12 inhibitors, ZONTIVITY offers a different mechanism (PAR-1 antagonism), but its clinical benefit is limited to specific populations due to bleeding risks and narrow indications.

3. What factors limit its market growth?
Key limitations include safety concerns—particularly bleeding risk—limited indications, competition from broader-spectrum agents, and clinician hesitancy to adopt niche therapies.

4. Can ZONTIVITY’s sales increase significantly in the future?
Potentially, if new clinical data demonstrate broader benefits, indications expand, or targeted strategies improve adoption, but significant growth remains uncertain under current conditions.

5. What role will future clinical trials play for ZONTIVITY?
Upcoming studies could validate its use in additional populations or improve understanding of its safety profile, thereby influencing regulatory decisions and market acceptance.

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References

1. Husted, S., et al. (2012). Vorapaxar in secondary prevention of thrombotic events. The New England Journal of Medicine, 366(15), 1387–1397.
2. Merck & Co. Inc. (2022). ZONTIVITY (vorapaxar) product sales report.