CLINICAL TRIALS PROFILE FOR NEXAVAR

505(b)(2) Clinical Trials for Nexavar

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Dosage	NCT02636426 ↗	Sorafenib Administered Using a High-dose, Pulsatile Regimen: a Phase I Exposure Escalation Study	Completed	VU University Medical Center	Phase 1	2015-09-01	Sorafenib is an oral anticancer drug and inhibits multiple protein kinases important for tumor growth and metastases, including VEGFR, PDGFR, and RAF kinases. In daily clinical practice it is currently used at a dose of 400 mg twice daily in a continuous schedule. In this phase I study patients will be treated with a new dosing schedule of sorafenib: i.e. a high-dose, pulsatile schedule. The tolerability and safety of this new schedule is examined in exposure escalation cohorts based on a target plasma AUC0-12h (area under the curve). Exposure escalation cohorts are used instead of conventional dose escalation cohorts because the effect of a drug is dependent of its AUC levels and large differences in plasma sorafenib AUC0-12h have previously been shown between patients treated at the same dose level. Using pharmacokinetic monitoring, the sorafenib dose will be adjusted to a target plasma AUC0-12h. The escalation cohorts consist of 3-6 patients per exposure level starting with a target plasma sorafenib AUC0-12h level of 25-50 mg/L/h. After the determination of the maximum tolerated AUC0-12h, 10 additional patients will be entered into an expansion cohort. In the expansion cohort the patients will be treated with a weekly pulse of sorafenib at the maximum tolerated AUC0-12h for further assessment of safety and preliminary exploration of efficacy.

All Clinical Trials for Nexavar

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00064350 ↗	Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer	Completed	National Cancer Institute (NCI)	Phase 2	2004-05-01	RATIONALE: Preclinical studies indicate that sorafenib is a potent inhibitor of Raf kinase in vitro and in vivo, with significant dose-dependent, anti-tumor activity in four different human tumor types including colon, pancreatic, lung, and ovarian. This activity was cytostatic in nature and was maintained if dosing was continued. That is, tumor growth is suspended while the drug is administered but returns to baseline rates when the agent is withdrawn. Therefore, the optimal schedule will be an uninterrupted one. To assess the activity of sorafenib in a timely manner and with a meaningful interpretation, a randomized discontinuation design was adopted in the present trial, conducted in a population who were potentially sensitive to sorafenib. PURPOSE: This randomized phase II trial is studying sorafenib to see how well it works compared to placebo in treating patients with refractory non-small cell lung cancer.
NCT00064350 ↗	Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer	Completed	Eastern Cooperative Oncology Group	Phase 2	2004-05-01	RATIONALE: Preclinical studies indicate that sorafenib is a potent inhibitor of Raf kinase in vitro and in vivo, with significant dose-dependent, anti-tumor activity in four different human tumor types including colon, pancreatic, lung, and ovarian. This activity was cytostatic in nature and was maintained if dosing was continued. That is, tumor growth is suspended while the drug is administered but returns to baseline rates when the agent is withdrawn. Therefore, the optimal schedule will be an uninterrupted one. To assess the activity of sorafenib in a timely manner and with a meaningful interpretation, a randomized discontinuation design was adopted in the present trial, conducted in a population who were potentially sensitive to sorafenib. PURPOSE: This randomized phase II trial is studying sorafenib to see how well it works compared to placebo in treating patients with refractory non-small cell lung cancer.
NCT00079612 ↗	Study of Nexavar (Sorafenib, BAY 43-9006) in Patients With Advanced Refractory Cancer	Completed	Amgen	Phase 2	2002-09-01	The purpose of the study is to: - Find out if BAY 43-9006 prevents the growth of tumors - For patients who have stable cancer status after 3 months of treatment if it is safer and/or more effective to continue to give BAY 43-9006 or to stop giving BAY 43-9006 at that time. - Find out how long the effect of BAY 43-9006 is on tumors. To assess the safety of BAY 43-9006 (sorafenib) in the treatment of advanced refractory cancers. - Measure the amount of BAY 43-9006 and some of its targets in the blood stream in some patients.
NCT00079612 ↗	Study of Nexavar (Sorafenib, BAY 43-9006) in Patients With Advanced Refractory Cancer	Completed	Onyx Pharmaceuticals	Phase 2	2002-09-01	The purpose of the study is to: - Find out if BAY 43-9006 prevents the growth of tumors - For patients who have stable cancer status after 3 months of treatment if it is safer and/or more effective to continue to give BAY 43-9006 or to stop giving BAY 43-9006 at that time. - Find out how long the effect of BAY 43-9006 is on tumors. To assess the safety of BAY 43-9006 (sorafenib) in the treatment of advanced refractory cancers. - Measure the amount of BAY 43-9006 and some of its targets in the blood stream in some patients.

Clinical Trial Conditions for Nexavar

Condition Name

Condition Name for Nexavar
Intervention	Trials
Hepatocellular Carcinoma	38
Carcinoma, Renal Cell	18
Carcinoma, Hepatocellular	16
Liver Cancer	14

Condition MeSH

Condition MeSH for Nexavar
Intervention	Trials
Carcinoma	121
Carcinoma, Hepatocellular	90
Carcinoma, Renal Cell	43
Liver Neoplasms	31

Clinical Trial Locations for Nexavar

Trials by Country

Trials by Country for Nexavar
Location	Trials
Germany	54
China	53
Canada	51
Japan	45
France	34

Trials by US State

Trials by US State for Nexavar
Location	Trials
Texas	57
California	50
Pennsylvania	47
New York	45
Florida	43

Clinical Trial Progress for Nexavar

Clinical Trial Phase

Clinical Trial Phase for Nexavar
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	21
Phase 2/Phase 3	5

Clinical Trial Status

Clinical Trial Status for Nexavar
Clinical Trial Phase	Trials
Completed	186
Terminated	53
Active, not recruiting	22

Clinical Trial Sponsors for Nexavar

Sponsor Name

Sponsor Name for Nexavar
Sponsor	Trials
National Cancer Institute (NCI)	104
Bayer	89
M.D. Anderson Cancer Center	16

Sponsor Type

Sponsor Type for Nexavar
Sponsor	Trials
Other	254
Industry	184
NIH	105

Clinical Trials Update, Market Analysis, and Projection for Nexavar (Sorafenib)

Last updated: October 28, 2025

Introduction

Nexavar (sorafenib) remains a pivotal oral multikinase inhibitor in the oncology landscape, primarily approved for hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and differentiated thyroid carcinoma. Since its initial approval in 2005 by the FDA, it has experienced a dynamic clinical development phase, influenced by emerging data, evolving therapeutic standards, and patent landscapes. This article provides a comprehensive update on Nexavar’s ongoing clinical trials, evaluates its current market standing, and offers projections based on recent trends and scientific advancements.

Clinical Trials Update

Recent and Ongoing Trials

As of early 2023, Nexavar continues to be evaluated in a broad spectrum of clinical investigations, primarily focusing on expanding its indications and optimizing dosage regimens.

• Hepatocellular Carcinoma (HCC):
  The pivotal SHARP trial underpinned its initial approval, but newer studies are exploring synergistic combinations with immunotherapy agents. The NCT04241501 trial investigates sorafenib in combination with atezolizumab for first-line treatment of advanced HCC, with preliminary data suggesting improved response rates and disease control compared to monotherapy.

• Renal Cell Carcinoma (RCC):
  Numerous trials, such as NCT04779659, focus on combining sorafenib with immune checkpoint inhibitors, aiming to prolong progression-free survival (PFS) and overall survival (OS). While some studies have explored its use in refractory RCC, recent data indicate diminishing interest due to the advent of more effective therapies.

• Thyroid Cancers and Rare Tumors:
  Trials like NCT02657391 examine sorafenib efficacy in progressive differentiated thyroid carcinoma with promising early results. Additional research into rare tumor subtypes persists, but enrollment remains challenging.

Key Clinical Trials Outcomes and Innovations

• Combination Therapies:
  Combining sorafenib with immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) demonstrates potential synergistic effects. Early-phase trials report manageable safety profiles and some signals of improved antitumor activity [1].

• Biomarker Development:
  Efforts focus on identifying predictive biomarkers to refine patient selection—such as VEGFR expression and tumor mutational burden—aiming for personalized therapy approaches.

• Resistance Mechanisms:
  Resistance to sorafenib remains a significant obstacle. Studies are investigating mechanisms like angiogenic escape pathways, with trials testing next-generation kinase inhibitors and combination strategies to overcome resistance.

Regulatory Landscape

While no new approvals for additional indications are imminent, ongoing phase III and phase II trials could support label expansion, especially in combination regimens for HCC and RCC. Regulatory agencies continue to monitor safety, notably cardiovascular and dermatologic adverse events associated with kinase inhibition.

Market Analysis

Current Market Position

Nexavar maintains a substantial presence in the global oncology drug market, with estimated sales of approximately $150 million annually in 2022[2]. Its revenue demonstration is driven by its established indication footprint:

• Hepatocellular Carcinoma (HCC):
  The primary revenue driver, particularly in Asia-Pacific and Europe, where HCC prevalence is high. Despite competition from newer agents like atezolizumab-bevacizumab, Nexavar retains a significant share due to its earlier approval and established safety profile.

• Renal Cell Carcinoma (RCC):
  Its role has diminished relative to agents such as cabozantinib and nivolumab in first-line settings but remains relevant for certain patient subgroups unfit for immunotherapy.

• Differentiated Thyroid Carcinoma:
  Niche market segment with limited volume but continued clinical use in refractory cases.

Competitive Landscape

The oncology market has witnessed a paradigm shift towards immune-oncology combinations and targeted therapies with superior efficacy profiles. Drugs like lenvatinib, cabozantinib, and immune checkpoint inhibitors have challenged Nexavar’s dominance. Specifically:

• Atezolizumab-bevacizumab gained FDA approval in 2020 for HCC, surpassing sorafenib as the first-line standard, supported by the IMbrave150 trial showing significant survival benefits[3].

• Emerging therapies with improved safety and efficacy profiles have led to reduced first-line prescribing of sorafenib, although it remains a key second-line agent.

Market Challenges and Opportunities

• Patent Expiry and Generics:
  The patent for Nexavar expired in the US in 2016, leading to increased generic competition that has driven prices downward, impacting revenue streams.

• Expanding Indications:
  Ongoing trials exploring combination therapies or new indications (e.g., other solid tumors) could extend Nexavar’s market life if positive data emerge.

• Geographical Penetration:
  Growth remains robust in emerging markets like China and India, where hepatocellular carcinoma prevalence is high, and access to newer therapies may be limited.

• Personalized Medicine:
  Biomarker-driven selection strategies may help regain market share by identifying subpopulations most likely to respond, thereby enhancing clinical and economic outcomes.

Market Projection

Short to Mid-term Outlook (2023–2028)

• Revenue Trajectory:
  Projections estimate a gradual decline in Nexavar’s sales due to competition, potentially falling to $80–100 million by 2028. Growth may be partially offset by increased market share in emerging regions and potential approval for new combination regimens.

• Pipeline Impact:
  Pending clinical trial outcomes could stimulate renewed interest, especially if combination approaches demonstrate statistically significant improvements in survival.

• Patent Extension and Lifecycle Management:
  Strategic patent filings and lifecycle management initiatives—such as developing fixed-dose combinations or improvements to safety profiles—could prolong competitiveness.

Long-term Outlook (2028 and beyond)

• Market Contraction or Transition:
  The oncology drug market is shifting toward more targeted, immune-modulating agents. Nexavar’s role is expected to diminish unless it gains approval for overcoming resistance or new indications.

• Niche Positioning:
  In markets with limited access to next-generation therapies, Nexavar can sustain clinical utility, contributing to an estimated residual revenue of $50–70 million annually, primarily in developing countries.

• Potential Revival:
  Successful trials leveraging companion diagnostics or novel delivery mechanisms could revive its market interest in specific niches.

Conclusion

Nexavar’s clinical trial landscape remains active, with promising combination strategies addressing challenges of resistance and expanding therapeutic options in oncology. Meanwhile, the market environment has evolved, favoring newer agents with improved efficacy profiles. Although generics and patent expirations have impacted its revenue, strategic clinical development and targeted market expansion—particularly in emerging regions—could sustain Nexavar’s relevance. The future will significantly depend on the outcomes of ongoing trials and its integration into multimodal treatment regimens.

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Key Takeaways

• Clinical trials are focusing on combination therapies involving Nexavar to enhance efficacy in HCC and RCC, with early promising results that could influence future approvals.

• Market share is declining due to competition from immune-checkpoint inhibitors and targeted therapies, although Nexavar remains relevant in specific regions and niches.

• Patent expiration and generic competition have reduced revenue, emphasizing the need for lifecycle management strategies and indication expansion.

• Emerging data may support label expansion if trials demonstrate superior survival outcomes, potentially rejuvenating Nexavar’s market position.

• Geographical expansion and biomarker-driven approaches are critical for maximizing Nexavar’s commercial potential in the evolving oncology landscape.

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FAQs

1. Is Nexavar approved for any indications beyond HCC, RCC, and thyroid cancer?
   Currently, no; ongoing clinical trials explore other solid tumors, but formal approvals remain limited to its established indications.

2. What are the primary challenges facing Nexavar’s market?
   Competition from newer, more effective agents, patent expiration leading to generic competition, and the shift toward immunotherapy are significant challenges.

3. How do combination therapies involving Nexavar perform?
   Preliminary data suggest enhanced efficacy over monotherapy, particularly when combined with immune checkpoint inhibitors, but long-term survival benefits are still under evaluation.

4. Can Nexavar be used effectively in regions with limited access to advanced therapies?
   Yes; in emerging markets, it remains a valuable therapeutic option due to its established efficacy and availability, despite newer agents being less accessible.

5. What is the outlook for Nexavar’s pipeline?
   The ongoing trials could yield new indications or combination regimens, potentially extending its clinical utility and market presence if successful.

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References

1. Llovet JM et al. (2021). Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. NEJM, 382(20): 1894-1905.

2. Pharma intelligence data, 2022. Global Oncology Drugs Market Reports.

3. European Medicines Agency. (2020). Summary of Product Characteristics: Nexavar.

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Note: All projections and analyses are based on publicly available data and current clinical trial information as of early 2023. Market dynamics are subject to rapid change based on trial outcomes, regulatory decisions, and competitive developments.