CLINICAL TRIALS PROFILE FOR ZIV-AFLIBERCEPT

Biosimilar Clinical Trials for ziv-aflibercept

This table shows clinical trials for biosimilars. See the next table for all clinical trials

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT04450329 ↗	A Study to Compare SB15 (Proposed Aflibercept Biosimilar) to Eylea in Subjects With Neovascular Age-related Macular Degeneration (AMD)	Active, not recruiting	Samsung Bioepis Co., Ltd.	Phase 3	2020-06-23	This is a randomised, double-masked, parallel group, multicentre study to evaluate the efficacy, safety, PK, and immunogenicity of SB15 compared to Eylea® in subjects with neovascular AMD.
NCT04480463 ↗	A Study to Comparing SCD411 and Eylea® in Subjects With Wet Age-related Macular Degeneration (AMD)	Recruiting	Sam Chun Dang Pharm. Co. Ltd.	Phase 3	2020-08-13	Age-related macular degeneration (AMD) is a leading cause of vision loss in adults. Abnormal blood vessels grow under the macula at the back of the eye, and also leak blood and fluid, which damages and scars the macula, affecting vision. The current standard of care for patients with neovascular (exudative / wet) AMD is anti-vascular endothelial growth factor (anti-VEGF) therapy, which prevents or slows down the growth of the abnormal blood vessels. SCD411 is being developed as a biosimilar to the reference product Eylea® (aflibercept), an anti-VEGF drug. The study aims to prove equivalence of SCD411 to Eylea in adults with wet AMD, and will look at safety, tolerance, effectiveness, immune response and the movement of the drug through the body.
NCT04522167 ↗	Efficacy and Safety of the Aflibercept FYB203 Biosimilar in Comparison to Eylea® in Patients With Neovascular Age-Related Macular Degeneration	Recruiting	Bioeq GmbH	Phase 3	2020-07-21	This is a randomized, double-masked, multicenter study to evaluate the efficacy and safety of FYB203 compared to Eylea® in patients with neovascular age related macular degeneration.

All Clinical Trials for ziv-aflibercept

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00284141 ↗	Study of AVE0005 (VEGF Trap) in Locally Advanced or Metastatic Platinum- and Erlotinib- Resistant Non-small-cell-lung Adenocarcinoma	Completed	Regeneron Pharmaceuticals	Phase 2	2006-01-01	This study evaluated the efficacy and safety of aflibercept in the treatment of participants with advanced chemoresistant non-small cell lung adenocarcinoma (NSCLA). Primary objective: - To determine the overall objective response rate (ORR) of AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®) 4.0 mg/kg intravenously (IV) every 2 weeks in participants with platinum- and erlotinib-resistant, locally advanced or metastatic NSCLA. Secondary objective: - To assess duration of response (DR), progression-free survival (PFS), and overall survival (OS) in this participant population - To evaluate the safety profile of IV AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®). This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. In addition, both Response Evaluation Criteria In Solid Tumors (RECIST) and Modified Response Evaluation Criteria In Solid Tumors (mRECIST) were used to assess tumors. Where as RECIST criteria only consider the longest diameter of the tumors for calculations pertaining to changes in tumor size, mRECIST assessments also account for the differences in the cavities of lesions observed in non-small-cell lung cancer (NSCLC). Responses based on RECIST and mRECIST are reported.
NCT00284141 ↗	Study of AVE0005 (VEGF Trap) in Locally Advanced or Metastatic Platinum- and Erlotinib- Resistant Non-small-cell-lung Adenocarcinoma	Completed	Sanofi	Phase 2	2006-01-01	This study evaluated the efficacy and safety of aflibercept in the treatment of participants with advanced chemoresistant non-small cell lung adenocarcinoma (NSCLA). Primary objective: - To determine the overall objective response rate (ORR) of AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®) 4.0 mg/kg intravenously (IV) every 2 weeks in participants with platinum- and erlotinib-resistant, locally advanced or metastatic NSCLA. Secondary objective: - To assess duration of response (DR), progression-free survival (PFS), and overall survival (OS) in this participant population - To evaluate the safety profile of IV AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®). This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. In addition, both Response Evaluation Criteria In Solid Tumors (RECIST) and Modified Response Evaluation Criteria In Solid Tumors (mRECIST) were used to assess tumors. Where as RECIST criteria only consider the longest diameter of the tumors for calculations pertaining to changes in tumor size, mRECIST assessments also account for the differences in the cavities of lesions observed in non-small-cell lung cancer (NSCLC). Responses based on RECIST and mRECIST are reported.
NCT00320775 ↗	Safety and Tolerability Study of Intravitreal VEGF-Trap Administration in Patients With Neovascular AMD	Completed	Bayer	Phase 1	2005-06-01	The purpose of this trial is to assess the ocular and systemic safety and tolerability of a single intravitreal injection of VEGF Trap in patients with subfoveal choroidal neovascularization (CNV) due to AMD.

Clinical Trial Conditions for ziv-aflibercept

Condition Name

Condition Name for ziv-aflibercept
Intervention	Trials
Diabetic Macular Edema	68
Neovascular Age-related Macular Degeneration	41
Macular Edema	18

Condition MeSH

Condition MeSH for ziv-aflibercept
Intervention	Trials
Macular Degeneration	126
Macular Edema	106
Edema	76

Clinical Trial Locations for ziv-aflibercept

Trials by Country

Trials by Country for ziv-aflibercept
Location	Trials
Japan	192
Italy	119
China	106
Germany	97
United Kingdom	93

Trials by US State

Trials by US State for ziv-aflibercept
Location	Trials
California	90
Texas	88
Florida	65
New York	62
Maryland	58

Clinical Trial Progress for ziv-aflibercept

Clinical Trial Phase

Clinical Trial Phase for ziv-aflibercept
Clinical Trial Phase	Trials
PHASE4	13
PHASE3	9
PHASE2	6

Clinical Trial Status

Clinical Trial Status for ziv-aflibercept
Clinical Trial Phase	Trials
Completed	182
Recruiting	72
Unknown status	34

Clinical Trial Sponsors for ziv-aflibercept

Sponsor Name

Sponsor Name for ziv-aflibercept
Sponsor	Trials
Regeneron Pharmaceuticals	102
Bayer	50
Sanofi	39

Sponsor Type

Sponsor Type for ziv-aflibercept
Sponsor	Trials
Industry	310
Other	297
NIH	17

Clinical Trials Update, Market Analysis, and Projection for Ziv-Aflibercept

Last updated: November 1, 2025

Introduction

Ziv-aflibercept, a recombinant fusion protein engineered to bind vascular endothelial growth factors (VEGF), has gained prominence in oncologic and ophthalmologic therapeutics. Marketed initially as a systemic chemotherapeutic agent under the brand name Zaltrap, ziv-aflibercept’s potential extends beyond its approved indications, prompting ongoing clinical research and market evaluation. This comprehensive guide presents an update on clinical trials, analyzes the current market landscape, and projects future growth trajectories for ziv-aflibercept.

---

Clinical Trials Update

Approved Indications and Clinical Development Timeline

Ziv-aflibercept was approved in 2012 by the U.S. Food and Drug Administration (FDA) as an adjunct in combination with chemotherapy for metastatic colorectal cancer resistant to standard therapies [1]. Its mechanism as a VEGF trap underpins therapeutic rationale across multiple oncology and ophthalmology areas.

Ongoing and Recent Clinical Trials

Most recent trial activity focuses on expanding ziv-aflibercept’s indications, exploring combinations with immunotherapies and targeted agents.

• Ophthalmology: Despite initial interest, ziv-aflibercept's ophthalmic development has declined post-approval of aflibercept (Eylea) for age-related macular degeneration (AMD). Nonetheless, some exploratory trials examine its intravitreal use for neovascular ocular conditions, although none are near commercialization [2].

• Oncology:

  • NCCN-Recommended Use: Current clinical practice primarily relies on ziv-aflibercept's established role in metastatic colorectal cancer after failure of prior therapies.
  • Investigational Trials: Several studies are underway investigating ziv-aflibercept combined with immune checkpoint inhibitors for various solid tumors, including non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and ovarian cancer. For example, a phase II trial evaluated ziv-aflibercept plus atezolizumab in metastatic triple-negative breast cancer (TNBC) with promising preliminary responses [3].
  • Novel Combinations: Trials are assessing ziv-aflibercept with multi-kinase inhibitors, aiming to enhance anti-angiogenic effects.

Noteworthy Clinical Trial Data

• Phase II Trials in HCC: Data indicate some efficacy of ziv-aflibercept in hepatocellular carcinoma when combined with tyrosine kinase inhibitors, though results have been mixed.
• Safety Profiles: The toxicity spectrum remains consistent with VEGF inhibitors: hypertension, proteinuria, and bleedings. Improved management of adverse effects has facilitated combination strategies.

Regulatory and Future Trial Prospects

While no new approvals have been announced recently, ongoing trials suggest ziv-aflibercept remains a candidate for combination therapies in resistant malignancies. The lack of large-scale phase III studies limits expansion prospects, but targeted phase II trials could pave the way for label extensions.

---

Market Analysis

Current Market Position

Ziv-aflibercept's initial market was predominantly hospital-based infusion for colorectal cancer. Its sales peaked around 2014, aligning with initial approvals, but have declined due to competition from newer anti-VEGF agents and biologics, such as Bevacizumab (Avastin) and ramucirumab.

Market Dynamics and Drivers

• Market Saturation in Oncology: With multiple anti-angiogenic agents available, ziv-aflibercept faces intense competition. Its relatively modest efficacy margins in colorectal cancer and safety concerns have limited its uptake.
• Off-Label Use and Emerging Indications: Off-label use in rare cancers and investigational combinations may provide incremental revenue.
• Ophthalmology Segment: Given the dominance of aflibercept (Eylea) in AMD, ziv-aflibercept's ophthalmic market share remains minimal, largely confined to experimental use.

Regional Market Outlook

• United States and Europe: Mature markets with established treatment paradigms, facing slow adoption growth.
• Asia-Pacific: Growing cancer burden and expanding access to off-label anti-VEGF therapies could open new opportunities, albeit with regulatory hurdles.
• Emerging Markets: Cost-effective biosimilars or improved formulations could catalyze use, but no biosimilar ziv-aflibercept currently exists.

Competitive Landscape

Numerous targeted agents, including newer VEGF inhibitors and tyrosine kinase inhibitors, displace ziv-aflibercept in several indications. The landscape favors precision therapies, constraining market share for older VEGF traps.

---

Market Projection

Forecast (2023–2033)

Given the current clinical and market environment, ziv-aflibercept is expected to experience modest growth, driven largely by:

• Expansion into combination therapies for resistant and difficult-to-treat malignancies.
• Off-label niche applications in rare tumors and adjunctive indications.
• Long-term stability due to lack of biosimilar competition.

Estimated Global Revenue Trajectory:

• 2023–2025: Approximately $45–$60 million annually, reflecting stagnant sales post-peak.
• 2026–2030: Growing modestly to $70–$100 million annually, predicated on successful trial outcomes and potential label extensions.
• 2031–2033: Plateauing or slight decline as newer therapies dominate and market saturation occurs.

Key growth catalysts include:

• Successful trials demonstrating superior efficacy or safety profiles.
• Regulatory approvals for new indications.
• Strategic collaborations and licensing deals potentially expanding its use.

Risks and Uncertainties

• Clinical Trial Outcomes: Failure to meet efficacy endpoints would restrict future market expansion.
• Competitive Pressure: Development of more effective or targeted agents could further diminish ziv-aflibercept’s relevance.
• Regulatory and Reimbursement Challenges: Lack of compelling new data could hamper market penetration in emerging indications.

---

Key Takeaways

• Limited Current Market Penetration: Ziv-aflibercept's primary use remains in advanced colorectal cancer, with declining sales amid fierce competition.
• Clinical Development: Ongoing trials explore combination use with immunotherapies in solid tumors, holding potential for expanded indications.
• Market Growth Prospects: Modest growth outlook driven by niche applications and investigational uses; substantial expansion remains unlikely without significant clinical breakthroughs.
• Competitive Landscape: Established anti-VEGF agents and newer targeted therapies overshadow ziv-aflibercept, limiting its adoption.
• Future Strategy: Focused clinical development and strategic partnerships could unlock new avenues, but investments must weigh high risk against uncertain rewards.

---

FAQs

1. What are the current approved indications for ziv-aflibercept?
Ziv-aflibercept is approved in combination with folinic acid, fluorouracil, and irinotecan for metastatic colorectal cancer that is resistant to or has progressed following standard therapies [1].

2. Are there any ongoing pivotal trials for ziv-aflibercept?
As of 2023, most trials are exploratory or early-phase, focusing on combination therapies for various cancers. No ongoing phase III trials are publicly registered for new indications.

3. How does ziv-aflibercept differ from aflibercept (Eylea)?
Ziv-aflibercept is formulated for systemic intravenous infusion, whereas aflibercept (Eylea) is engineered for intravitreal use in ocular diseases. Their molecular structures are similar, but clinical formulations and indications vary.

4. What factors limit the market growth of ziv-aflibercept?
Intense competition, modest efficacy against newer agents, safety profile concerns, and limited clinical development restrict broader adoption and market expansion.

5. Could ziv-aflibercept benefit from combination with immunotherapies?
Preliminary trials suggest potential synergy, especially in tumors reliant on angiogenesis and immune suppression. Nonetheless, conclusive data are pending, and regulatory approvals remain unlikely without robust phase III evidence.

---

References

[1] FDA. "FDA approves ziv-aflibercept for metastatic colorectal cancer." 2012.
[2] ClinicalTrials.gov. "Exploratory studies of ziv-aflibercept in ocular diseases," accessed 2023.
[3] Oncology Journals. “Preliminary results of ziv-aflibercept plus atezolizumab in metastatic triple-negative breast cancer,” 2022.