CLINICAL TRIALS PROFILE FOR ADEFOVIR DIPIVOXIL

505(b)(2) Clinical Trials for ADEFOVIR DIPIVOXIL

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 Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Bristol-Myers Squibb	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Dupont Applied Biosciences	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Glaxo Wellcome	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.

All Clinical Trials for ADEFOVIR DIPIVOXIL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000843 ↗	The Safety and Effectiveness of Adefovir Dipivoxil in HIV-Infected Children	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	To evaluate the single-dose pharmacokinetic profile and acute toxicity of bis-POM PMEA ( adefovir dipivoxil ) in HIV-1 infected children, and to determine whether age-related differences exist. To ascertain dosages that may be suitable for a multiple-dose evaluation in this patient population. Although the oral bioavailability of PMEA ( adefovir ) is low, the prodrug bis-POM PMEA has resulted in increased bioavailability in adult patients in clinical trials. However, the safety and pharmacokinetic patterns of drugs in infants often differ from those of adults and the direction of the variation is not predictable. This study will assess these parameters of bis-POM PMEA in children.
NCT00000885 ↗	Treatment Success and Failure in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs: A Rollover Study for ACTG 320	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	Group A: To compare the time to confirmed virologic failure (2 consecutive plasma HIV-RNA concentrations of 500 copies/ml or more) between the treatment arms: abacavir (ABC) or placebo in combination with zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV). To evaluate the safety and tolerability of these treatment arms. [AS PER AMENDMENT 06/16/99: To compare the time to confirmed treatment failure, permanent discontinuation of treatment, or death between the treatment arms.] [AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable.] Group B: To compare the proportion of patients who achieve plasma HIV-1 RNA concentrations below 500 copies/ml, as assessed by the standard Roche Amplicor assay at Week 16, or to compare the absolute changes in plasma HIV-1 RNA concentrations at Week 16 across the treatment arms: ABC or approved nucleoside analogs and nelfinavir (NFV) or placebo in combination with efavirenz (EFV) and adefovir dipivoxil. To compare the safety and tolerability of these treatment arms. Group C: To monitor plasma HIV-1 RNA trajectory over time and determine the time to a confirmed plasma HIV-1 RNA concentration above 2,000 copies/ml on 2 consecutive determinations for patients treated with ZDV or stavudine (d4T) plus 3TC and IDV. Group D: To evaluate plasma HIV-1 RNA responses at Weeks 16 and 48. To evaluate the safety and tolerability of the treatment arms: ABC, EFV, adefovir dipivoxil, and NFV. This study explores new treatment options for ACTG 320 enrollees (and, if needed, a limited number of non-ACTG 320 volunteers) who have been receiving ZDV (or d4T) plus 3TC and IDV and are currently exhibiting a range of virologic responses. By dividing the study into the corresponding, nonsequential cohorts (Groups A, B, C, D), different approaches to evaluating virologic success, i.e., undetectable plasma HIV-1 RNA levels, and virologic failure, i.e., plasma HIV-1 RNA levels of 500 copies/ml or more [AS PER AMENDMENT 12/27/01: 200 copies/ml or more], are explored while maintaining long-term follow-up of ACTG 320 patients. [AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable. This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV (or d4T) plus 3TC plus IDV.]
NCT00000892 ↗	A Study of Several Anti-HIV Drug Combinations in HIV-Infected Patients Who Have Used Indinavir	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To compare the proportion of patients whose plasma HIV-1 RNA is below 500 copies/ml after 16 weeks of treatment. To assess the safety, toxicity, and tolerance of each treatment arm. While indinavir is currently the most commonly prescribed protease inhibitor, the optimal therapy for a person on an indinavir-containing regimen who experiences a rebound in viral load or never experiences a decrease in viral load below 500 copies per milliliter is unknown. Current clinical practice for such patients typically involves empiric use of a combination of other protease inhibitors (saquinavir/nelfinavir or saquinavir/ritonavir) and at least 1 other antiretroviral agent to which the patient has had little or no prior exposure. This may involve the use of 1 or more reverse transcriptase inhibitors (RTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs). This study attempts to formally evaluate some of these options in indinavir-experienced patients.

Clinical Trial Conditions for ADEFOVIR DIPIVOXIL

Condition Name

Condition Name for ADEFOVIR DIPIVOXIL
Intervention	Trials
Chronic Hepatitis B	28
HIV Infections	21
Hepatitis B	17

Condition MeSH

Condition MeSH for ADEFOVIR DIPIVOXIL
Intervention	Trials
Hepatitis B	57
Hepatitis	54
Hepatitis A	49

Clinical Trial Locations for ADEFOVIR DIPIVOXIL

Trials by Country

Trials by Country for ADEFOVIR DIPIVOXIL
Location	Trials
United States	252
China	59
Canada	13
Korea, Republic of	12
Australia	11

Trials by US State

Trials by US State for ADEFOVIR DIPIVOXIL
Location	Trials
California	25
New York	21
Maryland	18
Massachusetts	13
Texas	13

Clinical Trial Progress for ADEFOVIR DIPIVOXIL

Clinical Trial Phase

Clinical Trial Phase for ADEFOVIR DIPIVOXIL
Clinical Trial Phase	Trials
Phase 4	20
Phase 3	17
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for ADEFOVIR DIPIVOXIL
Clinical Trial Phase	Trials
Completed	58
Unknown status	11
Terminated	4

Clinical Trial Sponsors for ADEFOVIR DIPIVOXIL

Sponsor Name

Sponsor Name for ADEFOVIR DIPIVOXIL
Sponsor	Trials
Gilead Sciences	24
GlaxoSmithKline	13
National Institute of Allergy and Infectious Diseases (NIAID)	10

Sponsor Type

Sponsor Type for ADEFOVIR DIPIVOXIL
Sponsor	Trials
Industry	66
Other	42
NIH	11

Clinical Trials Update, Market Analysis, and Projection for Adefovir Dipivoxil

Last updated: October 27, 2025

Introduction
Adefovir Dipivoxil, marketed primarily under the brand Hepsera, is an antiviral medication approved for the treatment of chronic hepatitis B virus (HBV) infection. As the landscape of hepatitis B therapeutics evolves, ongoing clinical research, market dynamics, and future projections are critical in guiding stakeholders’ strategic decisions. This article provides an exhaustive analysis of recent clinical trials, market performance, and the anticipated trajectory of Adefovir Dipivoxil in the global healthcare industry.

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Clinical Trials Update

Current Clinical Research Landscape

Adefovir Dipivoxil's original approval was based on clinical data demonstrating its efficacy in suppressing HBV DNA levels and promoting biochemical and histologic improvements in patients with chronic hepatitis B. Although its market presence has been somewhat overshadowed by newer agents such as tenofovir and entecavir, ongoing clinical trials aim to elucidate its role in combination therapies, formulations, and resistant cases.

Phase IV and Post-Marketing Surveillance

While no new Phase I-III trials are actively recruiting, Phase IV post-marketing studies continue to monitor long-term safety and efficacy. Key focus areas include potential nephrotoxicity, a known adverse effect, and resistance development. Recent studies have reinforced the safety profile, notably emphasizing renal function monitoring in long-term use.

Emerging Research and Adjunct Use

Recent trials are exploring Adefovir Dipivoxil's utility against HBV resistance strains and its comparative effectiveness in specific populations. For example, a 2022 study examined its efficacy as part of combination regimens in patients with lamivudine-resistant HBV, revealing moderate success but highlighting resistance challenges [1].

Innovations and Formulation Developments

Efforts are underway to improve pharmacokinetics and reduce toxicity. Novel formulations, such as extended-release tablets, are under preliminary scrutiny. Though no major new formulations have reached late-stage trials, ongoing research indicates potential for optimizing dosing regimens.

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Market Analysis

Historical Market Performance

Adefovir Dipivoxil was introduced in the early 2000s, capturing significant market share as one of the first oral nucleoside analogues for HBV. Its sales peaked in the late 2000s, facilitated by its affordability relative to newer therapies. However, its market share has waned due to safety concerns and the advent of more potent, less toxic agents.

Current Market Dynamics

Today, Adefovir Dipivoxil faces stiff competition from drugs like tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir. These alternatives offer superior efficacy and safety profiles, leading to reduced prescriptions of Adefovir Dipivoxil, especially in developed markets. Nonetheless, it remains relevant in resource-limited settings due to its cost-effectiveness and patent status affiliations.

Geographical Distribution

Asia-Pacific remains the dominant market for Adefovir Dipivoxil, with high hepatitis B prevalence in countries such as China, India, and Indonesia. Governments and healthcare providers often prioritize affordable therapies, ensuring continued use of generic formulations.

Regulatory and Patent Status

Adefovir Dipivoxil's patent expired in most jurisdictions by the early 2010s, resulting in increased generic manufacturing. Regulatory agencies continue to monitor safety but have not restricted its availability, sustaining a stable supply chain.

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Market Projection and Future Outlook

Short to Medium-Term (Next 5 Years)

Market analysts project a gradual decline in Adefovir Dipivoxil's global sales due to competitive pressures, particularly from drugs offering better safety profiles and once-daily dosing convenience. However, in low-income regions, it is expected to maintain steady demand until more cost-effective, yet equally efficacious, alternatives emerge.

Long-Term Outlook (Next 10-15 Years)

The long-term trajectory indicates a potential phase-out in high-income markets, replaced by newer agents such as TAF, which exhibits reduced nephrotoxicity and bone density impacts. Nonetheless, regional disparities will persist; in areas with limited healthcare infrastructure and high HBV prevalence, Adefovir Dipivoxil will likely remain a staple until health system upgrades occur.

Potential Growth Opportunities

Limited opportunities exist for repositioning Adefovir Dipivoxil owing to the dominance of superior drugs. However, niche applications may include combination therapies for resistant HBV strains or formulations targeting specific patient demographics.

Market Drivers and Barriers

Key drivers include cost advantages, extensive clinical history, and existing generic manufacturing capacity. Barriers encompass safety concerns, competitive efficacy, and the evolution of HBV treatment guidelines favoring tenofovir and entecavir.

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Conclusion

Adefovir Dipivoxil's clinical development landscape is mature, with ongoing post-marketing surveillance confirming its continued safety in selected populations. Its market presence is primarily sustained by economic factors and regional health policies rather than innovation-driven demand. Anticipated decline in global sales aligns with therapeutic advancements and improved treatment standards. Strategic players should consider these modalities when evaluating long-term investments or formulary placements involving Adefovir Dipivoxil.

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Key Takeaways

• Clinical Efficacy & Safety: It remains effective for certain HBV populations but shows limitations due to toxicity and resistance concerns.
• Market Dynamics: Declining global relevance in favor of newer agents with better safety profiles, yet stable in resource-limited regions.
• Regulatory & Patent Status: Widely available as a generic, facilitating affordable access but reducing incentives for innovation.
• Future Growth: Limited; primarily driven by regional needs and potential niche applications rather than broad market expansion.
• Strategic Outlook: Companies should monitor ongoing research for combination therapies and formulations, while policymakers should weigh cost-effectiveness against safety in HBV management.

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FAQs

1. Is Adefovir Dipivoxil still recommended as a first-line treatment for hepatitis B?
   No. Due to its inferior efficacy and nephrotoxicity risk compared to tenofovir and entecavir, it is generally considered a second-line agent or alternative in resource-limited settings.

2. What are the main safety concerns associated with Adefovir Dipivoxil?
   Renal toxicity and potential for resistance development are primary concerns. Regular renal function monitoring is essential during therapy.

3. Will Adefovir Dipivoxil become obsolete in the next decade?
   Likely in high-income markets, as newer, safer drugs dominate. However, it may persist in low-income regions until newer therapies become affordable and accessible.

4. Are there ongoing efforts to improve Adefovir Dipivoxil formulations?
   Preliminary research on extended-release and combination formulations is underway, but no significant advanced developments have been announced recently.

5. Could Adefovir Dipivoxil play a role in future HBV combination therapies?
   Potentially, especially for resistant strains or specific patient populations, but clinical trial evidence is needed to justify such use.

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References

[1] Xu, Y., et al. (2022). "Efficacy of Adefovir Dipivoxil in Lamivudine-Resistant HBV: A Clinical Trial." Journal of Hepatology Advances.