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.
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	Gilead Sciences	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.
NCT00000912 ↗	A Study on Amprenavir in Combination With Other Anti-HIV Drugs in HIV-Positive Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	The purpose of this study is to compare 4 different combinations of anti-HIV drugs and to determine the number of people whose HIV blood levels decrease to 200 copies/ml or less while on the treatment. This study evaluates the safety of these drug combinations, which include an experimental protease inhibitor (PI), amprenavir. Despite the success that many patients have had with PI treatment regimens, there is still a possibility that patients receiving PIs may continue to have high HIV blood levels. Because of this possibility, alternative drug combinations containing PIs are being studied. It appears that amprenavir, when taken with 3 or 4 other anti-HIV drugs, may be effective in patients with prior PI treatment experience.
NCT00001082 ↗	The Safety and Effectiveness of Adefovir Dipivoxil in the Treatment of HIV-Infected Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1996-12-01	To evaluate the safety and efficacy of adefovir dipivoxil in prolonging survival of patients with advanced HIV disease. In CMV prophylaxis substudy: To evaluate the efficacy of adefovir dipivoxil in preventing the development of CMV end-organ disease in patients with advanced HIV coinfected with CMV. The optimal treatment for HIV infection and the prevention of CMV disease has not been identified. Currently available antiretroviral therapies are hampered by both significant toxicities and the development of resistance. In addition, agents for preventing CMV disease, such as oral ganciclovir, are complicated by poor bioavailability and decreased compliance secondary to toxicities. Moreover, discordant results have been reported regarding the effectiveness of oral ganciclovir for preventing CMV disease. There is a need for newer agents with anti-HIV and anti-herpesvirus activity that have good pharmacokinetic and safety profiles and that will be well tolerated by patients. Adefovir dipivoxil is an oral pro-drug of PMEA, a nucleoside analog with activity against a broad spectrum of retroviruses and herpesviruses, including important human pathogens, such as HIV-1, HIV-2 and CMV. Due to its anti-HIV and anti-herpesvirus activity, adefovir dipivoxil may be able to decrease the incidence of opportunistic herpesvirus infections and prolong survival in patients with advanced HIV infection.
NCT00001087 ↗	The Effectiveness of Nelfinavir and Efavirenz, Used Alone or Together, Combined With Other Anti-HIV Drugs in Patients Who Have Taken Anti-HIV Drugs	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	Steps I and II: The purpose of this study is the following: To look at how many patients achieve undetectable HIV blood levels at Week 16. To look at the absolute change in HIV blood levels from the beginning of the study to Week 16. To look at the safety and tolerability of nelfinavir (NFV) and efavirenz (EFV) when used in combination or separately in regimens containing reverse transcriptase inhibitors (RTIs). For the 2 extension studies (Weeks 49 to 144): To look at the proportion of patients whose long-term viral load remains undetectable at Week 96. To look at the time from the beginning of the study to treatment failure, with patients evaluated through Week 144. Step III: To look at the proportion of patients whose HIV blood levels are undetectable 16 weeks after starting the salvage study treatment. To assess safety, toxicity, and tolerance of salvage study drug treatment. (This study has been changed by adding new objectives.) Achieving viral suppression has been widely endorsed as the primary goal of HIV therapy. However, there are few established guidelines for devising combinations of different classes of drugs which will enhance the potential for achieving viral suppression, reducing the risk of toxicity, and preserving therapeutic options for future use. This study includes 2 anti-HIV drugs, NFV (a protease inhibitor [PI]) and EFV (a nonnucleoside reverse transcriptase inhibitor [NNRTI]), for use either alone or in combination with RTI therapy for the purpose of limiting HIV replication. Patients with treatment failure at Week 16 choose 1 of the following 3 alternative salvage therapies: 2-drug PI regimen (saquinavir and ritonavir) plus adefovir dipivoxil and L-carnitine; EFV or NFV (if not already given) plus 2 new approved anti-HIV drugs outside the study; or the best available treatment outside the study. The new RTI, adefovir dipivoxil, is added to the 2-drug PI regimen to achieve suppression of viral replication and thereby delay disease progression. (This rationale reflects a change in the treatment given to patients with treatment failure at Week 16.)
NCT00002128 ↗	Phase I Study of the Safety, Tolerance, and Pharmacokinetics of 9-[2-(Bispivaloyloxymethyl)Phosphonylmethoxyethyl]Adenine (Bis-POM PMEA; Adefovir Dipivoxil) in HIV-Infected Patients	Completed	Gilead Sciences	Phase 1	1969-12-31	To study the safety, tolerance, and pharmacokinetics of a single dose of bis-POM PMEA (adefovir dipivoxil) when administered by the oral route in patients with HIV infection.

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
Hepatitis B, Chronic	9

Condition MeSH

Condition MeSH for ADEFOVIR DIPIVOXIL
Intervention	Trials
Hepatitis B	57
Hepatitis	54
Hepatitis A	49
Hepatitis B, Chronic	44

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
Withdrawn	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

Last updated: July 25, 2026

Adefovir Dipivoxil Clinical Trials Update, Market Analysis, and Ex-Factory Revenue Projections (US and Key Ex-US Markets)

Adefovir dipivoxil is an older oral nucleotide analog for chronic hepatitis B (CHB). Trial activity is now minimal relative to first-wave development, with the competitive landscape driven by next-generation CHB antivirals and generics. Commercial upside is constrained by established treatment guidelines that favor higher-barrier agents and by price erosion from generic entry in multiple jurisdictions.

Bottom line: Near-term market growth is limited; the addressable market shifts toward discounted generic share rather than new branded expansion. Revenue projection is therefore modeled as (1) shrinking/bounded total CHB drug spend growth, (2) continued substitution toward higher-efficacy/higher-genetic barrier agents, and (3) ongoing generic price compression.

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What clinical trials exist for adefovir dipivoxil in chronic hepatitis B and what is their current status?

Featured snippet answer: The core evidence base is from earlier CHB pivotal and dose-optimization studies (mid-2000s). Current public trial enrollment for new interventional studies is low, with most activity limited to retrospective analyses, long-term follow-up, or trials focused on combination/real-world endpoints rather than registrational programs.

Which endpoints defined the pivotal evidence base

Across the pivotal CHB program, efficacy and durability were anchored on:

• HBV DNA suppression (HBeAg-positive and HBeAg-negative cohorts)
• Biochemical response (ALT normalization)
• Virologic breakthrough rates over time
• Resistance emergence (adefovir resistance markers)

Long-term follow-up emphasized:

• Cumulative resistance risk with prolonged therapy
• Sustained suppression and treatment discontinuation outcomes (in limited settings)

How are trial results typically framed for current decision-making

For modern CHB treatment selection, clinicians weigh:

• Virologic response depth and durability
• Resistance profile and real-world breakthrough incidence
• Renal safety considerations in long-duration therapy

These factors drove displacement of adefovir by agents with better efficacy-resistance balance in many guidelines and practice patterns.

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When did adefovir dipivoxil lose exclusivity and how does that affect clinical and commercial investment?

Featured snippet answer: Adefovir dipivoxil’s branded exclusivity has long ended, and generic entry drove a major shift from branded clinical investment to cost-driven utilization and guideline-based substitution.

Why exclusivity expiration changes trial behavior

Post-exclusivity, sponsors typically avoid:

• New large, registrational Phase 3 programs
• Expensive development where guideline adoption is declining

Instead, the focus shifts to:

• Post-marketing safety surveillance
• Label maintenance and formulation lifecycle management
• Limited comparative studies where clinically necessary

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What is the Orange Book status of adefovir dipivoxil and what does that imply for generic entry risk?

Featured snippet answer: In the US, adefovir dipivoxil is widely available as a generic product; the regulatory path is not a major gating factor for near-term supply, but price erosion and channel competition are.

Generic entry implications

For CHB nucleos(t)ide analogs:

• Once generics are fully established, competitive risk moves from “can generics enter” to “can they hold share at low prices.”
• Litigation and Paragraph IV risk are generally historical for older products with established generic competition.

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What patents protect adefovir dipivoxil and how strong is the patent estate today?

Featured snippet answer: The patent estate for adefovir dipivoxil is largely expired or otherwise non-blocking for new generic manufacturing, given the age of the product and broad generic availability.

Practical effect on market structure

When the core compound and standard formulations are no longer meaningfully protected:

• Competitive differentiation falls to distribution, rebates, and contracting
• New lifecycle IP (if any) has limited impact because CHB regimens already favor other antivirals

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How does adefovir dipivoxil compare with modern chronic hepatitis B standards of care (tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir)?

Featured snippet answer: Adefovir is generally considered behind first-line modern options because guideline-preferred regimens prioritize stronger efficacy and lower resistance risk, with renal safety profiles optimized via drug selection and monitoring.

Relative positioning by decision drivers

• Efficacy depth and durability: modern agents typically show higher rates of deep virologic response over time
• Resistance barrier: newer therapies are favored to minimize resistance events
• Renal safety: adefovir is associated with nephrotoxicity risk signals that matter in long-duration CHB treatment, shifting preference toward alternatives with improved renal tolerability in many patients

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Which companies are selling adefovir dipivoxil and what is the likely competitive landscape in 2025-2028?

Featured snippet answer: The market is dominated by generic manufacturers and distributors; brand-focused competition is not the key driver. Competitive intensity is primarily price and contracting-led.

How the market typically clears for older CHB generics

• Wholesale acquisition cost and net price compression continue
• Patient and prescriber selection increasingly follows guideline preference and historical tolerability/renal factors
• Tender-based hospital procurement and pharmacy benefit dynamics determine realized price

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What market size can adefovir dipivoxil address and how much revenue is at risk from guideline substitution?

Featured snippet answer: The addressable volume is residual: adefovir persists primarily in patients already on therapy, those with contraindications to preferred agents, and regions where alternative access and reimbursement differ.

Revenue model structure

Revenue projection is modeled as:

Ex-factory revenue = (Treated patients) × (Average annual treatment cost net of generic price) Where:

• Treated patients decline or shift due to substitution to preferred agents.
• Average annual cost continues to fall due to competitive generics.

Projection logic for 2025-2028

Because global CHB treatment is mature and guideline-driven:

• Total CHB treated population is relatively stable to modestly growing (new diagnoses plus ongoing treatment), but
• Drug selection increasingly favors:
  • tenofovir-based options (with careful renal selection)
  • entecavir in certain patient subsets
• Therefore, adefovir’s share declines faster than total CHB treated volume.

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Adefovir dipivoxil revenue projections: base case, downside, and upside

Featured snippet answer: Revenue is likely to remain low-to-modest and trend downward in the base case due to continued substitution and price compression; any upside requires a slower-than-expected share erosion or region-specific access constraints for preferred competitors.

Assumptions (high-level, scenario-based)

• Base case: continued share loss, net price compression at a moderate pace
• Downside: faster substitution to preferred agents and deeper price pressure
• Upside: slower substitution and stabilization of generic net pricing

US plus selected Ex-US markets (projection table)

Note: figures are directionally consistent with an older generic CHB asset; exact ex-factory totals depend on country-level tender dynamics and payer policy.

Scenario	2025 Ex-factory Revenue (USD)	2026	2027	2028	CAGR (2025-2028)
Downside	40–55M	35–48M	30–42M	25–38M	-10% to -15%
Base case	55–75M	50–70M	45–63M	40–58M	-5% to -9%
Upside	75–95M	70–90M	65–85M	60–80M	-2% to -5%

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What clinical development is left for adefovir dipivoxil (new trials, new indications, or formulation work)?

Featured snippet answer: No clear registrational development program is currently expected; remaining activity typically involves post-marketing evidence, safety monitoring, and limited formulation lifecycle work.

What “new” studies usually look like

For legacy CHB antivirals, ongoing publication patterns often include:

• Renal safety in real-world cohorts
• Resistance evolution under long-duration treatment
• Switch outcomes from adefovir to other agents
• Population sub-analyses (age, baseline kidney function, comorbidities)

These studies inform practice but generally do not create a new growth curve.

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What biosimilar or biologic competition is relevant to adefovir dipivoxil?

Featured snippet answer: None. Adefovir dipivoxil is a small-molecule antiviral; competitive risk comes from other nucleos(t)ide analogs, not biosimilars.

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What patient switch dynamics affect adefovir dipivoxil demand?

Featured snippet answer: Switch demand tends to increase as patients move toward preferred agents due to:

• perceived efficacy advantages
• renal safety optimization
• resistance avoidance strategies

Switch drivers

• Rising HBV DNA breakthrough or inadequate suppression
• Renal function decline during long-term therapy
• Physician-driven regimen optimization aligned with guideline updates

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Which regions have the highest residual demand for adefovir dipivoxil and why?

Featured snippet answer: Residual demand is typically strongest where:

• CHB treatment access is uneven across preferred newer agents
• payer/health-system procurement favors older generics
• historical prescribing patterns persist

Regional demand mechanics

• Tender-driven markets: older generics can persist through procurement cycles even if guidelines shift.
• Reimbursement constraints: preferred therapies may be less accessible, keeping legacy antivirals in use.
• Physician familiarity: long-term patients are less likely to switch without a clinical trigger.

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What generic entry risks exist for adefovir dipivoxil (manufacturing, IP barriers, regulatory leverage)?

Featured snippet answer: For a fully generic, established product, the main “risk” is not patent blocking but margin compression from additional low-cost supply and regulatory inspections affecting manufacturing continuity.

Manufacturing/IP barrier reality

• Standard generic production is feasible for an established small molecule.
• Regulatory leverage is more about facility readiness and product quality rather than IP.

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Key Takeaways

• Adefovir dipivoxil’s clinical development is largely historical; current activity is mainly post-marketing, long-term follow-up, and real-world evidence.
• Commercially, it behaves like a mature generic CHB asset facing steady guideline-led substitution to preferred nucleos(t)ide analogs.
• Revenue is expected to remain limited and trend downward in the base case from share erosion plus ongoing generic price compression.
• The competitive battlefield is tender and contracting-driven, not new clinical claims.

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FAQs

1) Why is adefovir dipivoxil less preferred than newer hepatitis B antivirals?

Guidelines tend to favor agents with stronger durability, lower resistance risk, and more favorable long-duration safety considerations, shifting prescribing away from adefovir.

2) What patient groups are most likely to stay on adefovir long term?

Patients already treated on stable regimens, those with contraindications to preferred alternatives, and settings where older generics remain reimbursed.

3) Does resistance still matter for current adefovir use?

Yes. Resistance risk is a key historical driver of switch decisions, especially in patients with inadequate suppression over time.

4) Is there any meaningful new indication development for adefovir dipivoxil?

No major new registrational indications are evident for this legacy CHB antiviral.

5) What is the main threat to adefovir dipivoxil revenue over the next few years?

Continued substitution toward tenofovir- and entecavir-based regimens and additional price pressure from generic competition.

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References

1. Bloomberg Law and related pharmaceutical IP/Orange Book compendiums (accessed for general market context).
2. FDA Orange Book data for active ingredient listings and approval history (accessed for general generic status context).
3. AASLD/EASL hepatitis B management guidance (guideline-driven prescribing context).