Ziv-aflibercept - Biologic Drug Details

Summary for ziv-aflibercept

Tradenames:	1
High Confidence Patents:	0
Applicants:	1
BLAs:	1
Suppliers: see list	1
Recent Clinical Trials:	See clinical trials for ziv-aflibercept

Recent Clinical Trials for ziv-aflibercept

Identify potential brand extensions & biosimilar entrants

Sponsor	Phase
Federation Francophone de Cancerologie Digestive	PHASE2
Tanta University	EARLY_PHASE1
EyeBiotech Ltd.	PHASE2

See all ziv-aflibercept clinical trials

Pharmacology for ziv-aflibercept

Mechanism of Action	Vascular Endothelial Growth Factor Inhibitors
Established Pharmacologic Class	Vascular Endothelial Growth Factor Inhibitor

Note on Biologic Patents

Matching patents to biologic drugs is far more complicated than for small-molecule drugs.

DrugPatentWatch employs three methods to identify biologic patents:

1. Brand-side disclosures in response to biosimilar applications

These patents were identified from disclosures by the brand-side company, in response to a potential biosimilar seeking to launch. They have a high certainty of blocking biosimilar entry. The expiration dates listed are not estimates — they're expiration dates as indicated by the brand-side company.

2. DrugPatentWatch analysis and brand-side disclosures

These patents were identified from searching drug labels and other general disclosures from the brand-side company. This list may exclude some of the patents which block biosimilar launch, and some of these patents listed may not actually block biosimilar launch. The expiration dates listed for these patents are estimates, based on the grant date of the patent.

3. Patents from broad patent text search

For completeness, these patents were identified by searching the patent literature for mentions of the branded or ingredient name of the drug. Some of these patents protect the original drug, whereas others may protect follow-on inventions or even inventions casually mentioning the drug. The expiration dates listed for these patents are estimates, based on the grant date of the patent.

1) High Certainty: US Patents for ziv-aflibercept Derived from Brand-Side Litigation

No patents found based on brand-side litigation

2) High Certainty: US Patents for ziv-aflibercept Derived from DrugPatentWatch Analysis and Company Disclosures

These patents were obtained from company disclosures

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Patent No.	Estimated Patent Expiration	Source
Sanofi-aventis U.s. Llc	ZALTRAP	ziv-aflibercept	Injection	125418	10,246,516	2036-11-18	DrugPatentWatch analysis and company disclosures
Sanofi-aventis U.s. Llc	ZALTRAP	ziv-aflibercept	Injection	125418	10,751,399	2038-03-20	DrugPatentWatch analysis and company disclosures
Sanofi-aventis U.s. Llc	ZALTRAP	ziv-aflibercept	Injection	125418	6,894,136	2024-05-04	DrugPatentWatch analysis and company disclosures

3) Low Certainty: US Patents for ziv-aflibercept Derived from Patent Text Search

These patents were obtained by searching patent claims

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Patent No.	Estimated Patent Expiration	Source
Sanofi-aventis U.s. Llc	ZALTRAP	ziv-aflibercept	Injection	125418	10,172,817	2037-06-22	Patent claims search
Sanofi-aventis U.s. Llc	ZALTRAP	ziv-aflibercept	Injection	125418	10,265,291	2037-02-13	Patent claims search
Sanofi-aventis U.s. Llc	ZALTRAP	ziv-aflibercept	Injection	125418	10,287,294	2036-07-08	Patent claims search

International Patents for ziv-aflibercept

Country	Patent Number	Estimated Expiration
Denmark	2928491
South Korea	20210063457
Australia	2019239730

Market Dynamics and Financial Trajectory for the Biologic Drug: Ziv-Aflibercept

Last updated: July 28, 2025

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Introduction

Ziv-aflibercept, marketed as Zaltrap®, is a recombinant fusion protein biologic developed by Sanofi. It functions as an angiogenesis inhibitor by acting as a decoy receptor for vascular endothelial growth factors (VEGF), intercepting pro-angiogenic signaling pathways crucial in tumor progression. Initially approved for metastatic colorectal cancer (mCRC), ziv-aflibercept's strategic positioning within oncology markets exemplifies the nuances of biologic drug dynamics, influenced by clinical efficacy, market competition, regulatory frameworks, and evolving therapeutic landscapes.

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Market Overview and Current Status

Ziv-aflibercept debuted in 2012, designed to augment standard chemotherapy regimens in mCRC patients resistant to initial therapies. Its initial market entry targeted a lucrative segment within the broader oncology biologic sphere, which has historically experienced rapid growth driven by the expanding prevalence of cancer, advances in biologic manufacturing, and a shift towards personalized medicine.

Despite its initial promise, ziv-aflibercept faces complex market conditions. FDA approval for ziv-aflibercept was specific to refractory mCRC, with approvals contingent upon demonstrated efficacy benefits, notably improvements in progression-free survival (PFS). The drug's positioning is further influenced by the competitive landscape, featuring multi-targeted anti-angiogenic biologics such as regorafenib and aflibercept (Eylea® for ophthalmology, but related biologic as a VEGF trap).

The drug's geographic footprint also impacts its market dynamics. While the U.S. remains an initial stronghold, uptake has matured in other territories where reimbursement policies and clinical guidelines influence adoption rates.

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Market Dynamics Influencing Ziv-Aflibercept

1. Competitive Landscape

The biologic anti-angiogenic market is densely populated. Bevacizumab (Avastin®) and aflibercept have established dominance in oncology, with more extensive clinical data and broader indications. The presence of multiple potent competitors constricts ziv-aflibercept’s market share, especially as newer agents with better safety and efficacy profiles emerge.

Furthermore, the development of immune checkpoint inhibitors and targeted therapies challenge traditional anti-angiogenic approaches, reshaping treatment paradigms in colorectal and other cancers. Clinicians' preferences are increasingly guided by efficacy, toxicity profiles, and combination strategies, impacting ziv-aflibercept's utilization.

2. Regulatory and Reimbursement Factors

Regulatory approvals are pivotal for market access. While the FDA approved ziv-aflibercept in 2012, subsequent regulatory reviews and label updates influence prescribing behaviors. Reimbursement policies, particularly in highly regulated markets like the U.S. and Europe, significantly determine patient access and prescribing protocols.

The cost-effectiveness of ziv-aflibercept remains under scrutiny, with payer policies favoring therapies with proven survival benefits and manageable toxicity profiles. Budget impact analyses advocate for sustained but cautious use within chemotherapy regimens, impacting long-term sales trajectories.

3. Clinical Efficacy and Safety Profile

Clinical trials have demonstrated ziv-aflibercept’s capacity to extend PFS and overall survival (OS) when combined with chemotherapy in refractory mCRC [1]. However, its toxicity profile, primarily hypertension and proteinuria, alongside infusion-related reactions, influences treatment adherence and clinician acceptance.

The emergence of data supporting combination regimens with other biologics or targeted therapies can potentially enhance efficacy but also complicate safety profiles, thereby influencing market dynamics.

4. Patent Status and Biosimilars

Biologics enjoy patent protection, with exclusivity often spanning 12-14 years post-launch. Ziv-aflibercept’s patent life trajectory impacts future market penetration by biosimilars. As biosimilars enter markets—particularly in regions with mature biologic markets—they exert downward pressure on prices, affecting ziv-aflibercept's financial trajectory.

However, biologics’ complex manufacturing processes and regulatory hurdles for biosimilar approval maintain some pricing power, especially in premium markets.

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Financial Trajectory Analysis

1. Revenue Trends

Initially, ziv-aflibercept experienced robust revenue growth in its target indication, driven by high unmet medical need and limited competition at launch. However, trend analyses indicate a plateau or slight decline in revenues, attributable to multiple factors:

• Market saturation within approved indications.
• Growing competition from alternative therapies.
• Limited expanded indications, constraining market expansion.

In 2021, Sanofi reported revenues from oncology biologics, including ziv-aflibercept, exhibiting modest growth or stability, though specific sales figures for ziv-aflibercept remain confidential [2].

2. Impact of Market Penetration and Adoption

Market penetration relies heavily on prescriber acceptance and reimbursement environments. In the U.S., physicians tend to favor established agents with more comprehensive data sets and broader indications. In emerging markets, higher unmet need drives some use, yet affordability remains a barrier.

Global adoption remains constrained by the drug's specificity to refractory mCRC and the availability of alternative therapies, resulting in a finite revenue horizon.

3. Future Revenue Projections

Projected revenue trajectories forecast a gradual decline over the next 5-7 years, influenced by:

• Patent expiration or biosimilar entry (~2030, assuming 12-year patent protection secured in 2018).
• Shifts toward targeted therapies and immunotherapies for colorectal and other solid tumors.
• Price erosion due to biosimilar competition and payer pressures.
• Potential label expansions or new indications, which could temporarily bolster sales.

Financial modeling suggests that ziv-aflibercept’s peak global sales may have been realized in the initial years post-launch, with a subsequent downward trend unless new growth avenues materialize.

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Strategic Opportunities and Challenges

Opportunities

• Indication Expansion: Clinical trials assessing ziv-aflibercept’s efficacy in other solid tumors (e.g., non-small cell lung cancer, ovarian cancer) could unlock new revenue streams.
• Combination Strategies: Synergistic regimens with immunotherapies or targeted agents may improve clinical outcomes, fostering market relevance.
• Geographic Expansion: penetration into underserved emerging markets, where existing anti-angiogenic options are limited, presents growth opportunities.

Challenges

• Competitive Price Pressures: Biosimilar entry and institutional preference for established agents threaten profit margins.
• Clinical Data Limitations: Limited large-scale phase III trials compared to competitors hamper clinical differentiation.
• Evolving Therapeutic Landscape: The rise of immunotherapies diminishes reliance on anti-angiogenic biologics in some indications.

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Key Takeaways

• Market saturation and stiff competition have constrained ziv-aflibercept’s revenue growth since launch, with a likely decline forecasted over the next decade.
• Biosimilar development and patent expiration are critical to future pricing strategies and market share.
• Therapeutic innovation, including combination strategies and indication expansion, remains crucial to maintaining relevance.
• Pricing and reimbursement policies are significant determinants of access and profitability, especially within heterogeneous global markets.
• Strategic diversification into emerging indications and geographies offers potential avenues for revitalization but requires robust clinical validation.

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FAQs

1. When was ziv-aflibercept approved, and for what indication?
Ziv-aflibercept, marketed as Zaltrap®, was approved by the FDA in August 2012 for use in combination with chemotherapy for metastatic colorectal cancer that is refractory to other treatments [1].

2. How does ziv-aflibercept differ from aflibercept (Eylea)?
Ziv-aflibercept and aflibercept share similar molecular structures but are formulated for different uses; ziv-aflibercept is optimized for oncologic indications, whereas aflibercept (Eylea®) is used for ophthalmic conditions, demonstrating the versatility of VEGF traps.

3. What are the primary competitors to ziv-aflibercept?
Main competitors include bevacizumab (Avastin®), ramucirumab, regorafenib, and other anti-angiogenic agents that target the VEGF pathway with broader or more validated indications.

4. What is the potential impact of biosimilars on ziv-aflibercept?
Biosimilars could substantially reduce prices and pressure market share, especially post-patent expiry, affecting the expected revenue trajectory of ziv-aflibercept.

5. Are there ongoing clinical trials to expand ziv-aflibercept’s indications?
As of current data, clinical trials are underway or planned exploring ziv-aflibercept's efficacy in other solid tumors, but clear expansion pathways depend on positive trial outcomes and regulatory approvals.

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References

1. Van Cutsem E, et al. (2012). "Ziv-aflibercept (Zaltrap®) in metastatic colorectal cancer." Lancet Oncology.
2. Sanofi Annual Report 2021. Sanofi.