CLINICAL TRIALS PROFILE FOR HEPSERA

All Clinical Trials for HEPSERA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00158704 ↗	Continued Access Study of Adefovir Dipivoxil (ADV) for Patients w/Chronic HBV Infection.	Terminated	Gilead Sciences	N/A	2002-01-01	Provide adefovir dipivoxil (Hepsera) 10 mg once daily to patients with chronic hepatitis B virus (HBV) infection who have completed a Gilead-sponsored study of adefovir dipivoxil and require continued access to adefovir dipivoxil.
NCT00158717 ↗	Observational Study of the Durability of Seroconversion Chronic HBV Patients Who Seroconverted in a Previous Gilead-Sponsored Study of ADV.	Completed	Gilead Sciences		2003-04-01	To investigate the durability of HBeAg seroconversion in patients with chronic hepatitis B virus infection (HBV) who have seroconverted while participating in a previous Gilead-sponsored study of adefovir dipivoxil.
NCT00230477 ↗	Hepsera Versus Hepsera Plus Lamivudine for Treatment of Chronic Hepatitis B in Patients With Normal ALT	Completed	Gilead Sciences	Phase 4	2003-04-01	This project is a randomized, open-label trial of adefovir dipivoxil (Hepsera) and lamivudine combination therapy versus adefovir dipivoxil (Hepsera) monotherapy. Both adefovir dipivoxil and lamivudine are nucleoside analogues approved by the U.S. FDA for the treatment of chronic hepatitis B. The primary hypothesis is that subjects treated with combination therapy will see their viral DNA count decrease in an amount greater than subjects treated with monotherapy. The secondary hypothesis is that subjects treated with combination therapy will have a higher HBeAg conversion rate compared to historical controls of subjects treated with lamivudine or adefovir dipivoxil monotherapy.
NCT00230477 ↗	Hepsera Versus Hepsera Plus Lamivudine for Treatment of Chronic Hepatitis B in Patients With Normal ALT	Completed	GlaxoSmithKline	Phase 4	2003-04-01	This project is a randomized, open-label trial of adefovir dipivoxil (Hepsera) and lamivudine combination therapy versus adefovir dipivoxil (Hepsera) monotherapy. Both adefovir dipivoxil and lamivudine are nucleoside analogues approved by the U.S. FDA for the treatment of chronic hepatitis B. The primary hypothesis is that subjects treated with combination therapy will see their viral DNA count decrease in an amount greater than subjects treated with monotherapy. The secondary hypothesis is that subjects treated with combination therapy will have a higher HBeAg conversion rate compared to historical controls of subjects treated with lamivudine or adefovir dipivoxil monotherapy.
NCT00230477 ↗	Hepsera Versus Hepsera Plus Lamivudine for Treatment of Chronic Hepatitis B in Patients With Normal ALT	Completed	University of Washington	Phase 4	2003-04-01	This project is a randomized, open-label trial of adefovir dipivoxil (Hepsera) and lamivudine combination therapy versus adefovir dipivoxil (Hepsera) monotherapy. Both adefovir dipivoxil and lamivudine are nucleoside analogues approved by the U.S. FDA for the treatment of chronic hepatitis B. The primary hypothesis is that subjects treated with combination therapy will see their viral DNA count decrease in an amount greater than subjects treated with monotherapy. The secondary hypothesis is that subjects treated with combination therapy will have a higher HBeAg conversion rate compared to historical controls of subjects treated with lamivudine or adefovir dipivoxil monotherapy.
NCT00307489 ↗	Treatment of Persistent Viremia (Virus in Blood) in Chronic Hepatitis B Subjects Already Receiving Adefovir Dipivoxil	Completed	Gilead Sciences	Phase 2	2006-03-01	This study explores the efficacy, safety and tolerability of tenofovir DF (TDF) 300 mg once daily monotherapy versus the combination of emtricitabine 200 mg plus tenofovir DF 300 mg (FTC/TDF) once daily in subjects currently being treated with adefovir dipivoxil (Hepsera) for chronic hepatitis B who have persistent viral replication (detectable hepatitis B virus deoxyribonucleic acid [HBV DNA]). Subjects with confirmed (within 4 weeks) plasma HBV DNA ≥ 400 copies/mL during double blind treatment at Week 24 or any time thereafter have the option of receiving 12 weeks of open-label FTC/TDF which may be continued through the end of the 168-week treatment period if there is a virologic response (HBV DNA < 400 copies/mL). Alternatively, subjects with confirmed HBV DNA < 400 copies/mL at or any time after Week 24 of double-blind treatment may continue blinded therapy up to Week 168 at the discretion of the investigator. If, in the investigator's opinion, it is felt that continued blinded treatment beyond 24 weeks in subjects with confirmed HBV DNA ≥ 400 copies/mL is not beneficial, the subject may discontinue the study and begin commercially available HBV therapy rather than initiate open-label FTC/TDF.

Clinical Trial Conditions for HEPSERA

Condition Name

Condition Name for HEPSERA
Intervention	Trials
Hepatitis B	7
Chronic Hepatitis B	5
Hepatitis B, Chronic	4
HBeAg(-) Chronic Hepatitis B With Compensated Liver Function	1

Condition MeSH

Condition MeSH for HEPSERA
Intervention	Trials
Hepatitis B	18
Hepatitis	15
Hepatitis B, Chronic	13
Hepatitis A	12

Clinical Trial Locations for HEPSERA

Trials by Country

Trials by Country for HEPSERA
Location	Trials
Korea, Republic of	11
United States	8
Hong Kong	3
Malaysia	2
Spain	2

Trials by US State

Trials by US State for HEPSERA
Location	Trials
New York	2
California	2
Connecticut	1
Virginia	1
Pennsylvania	1

Clinical Trial Progress for HEPSERA

Clinical Trial Phase

Clinical Trial Phase for HEPSERA
Clinical Trial Phase	Trials
Phase 4	7
Phase 3	4
Phase 2	2

Clinical Trial Status

Clinical Trial Status for HEPSERA
Clinical Trial Phase	Trials
Completed	13
Unknown status	3
Terminated	2

Clinical Trial Sponsors for HEPSERA

Sponsor Name

Sponsor Name for HEPSERA
Sponsor	Trials
Gilead Sciences	5
GlaxoSmithKline	4
Bristol-Myers Squibb	3

Sponsor Type

Sponsor Type for HEPSERA
Sponsor	Trials
Other	27
Industry	18

HEPSERA (adefovir dipivoxil) clinical trials update, market analysis, and projection

Last updated: May 23, 2026

HEPSERA is an older, off-patent antiviral (adefovir dipivoxil) with limited incremental clinical trial activity in the US and EU in recent years. Commercially, the product line’s revenue exposure is primarily tied to chronic hepatitis B (CHB) persistence and payer mix rather than new-use adoption, with declining utilization relative to newer first-line agents.

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What is HEPSERA (adefovir dipivoxil) and how is it used in chronic hepatitis B?

Quick answer: HEPSERA is a nucleotide analog reverse transcriptase inhibitor used for CHB. In practice, uptake has shifted toward higher-barrier, more potent regimens, which has reduced HEPSERA’s addressable market over time.

What dosing and formulation does HEPSERA have

• Dosage form: oral tablet
• Strength: 10 mg adefovir dipivoxil
• Regimen (typical labeling context): once daily dosing for CHB

What clinical endpoints matter most for HEPSERA

• Virologic response: HBV DNA suppression
• HBeAg status endpoints: HBeAg seroconversion (where applicable)
• Resistance: emergence of adefovir-associated resistance substitutions
• Safety: renal monitoring is a key pharmacovigilance topic for nucleotide analogs

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What clinical trials exist for HEPSERA and what is the latest update?

Quick answer: No broad, recent phase-3 program that would be expected to drive a new commercial cycle is publicly prominent for HEPSERA in major registries, reflecting its mature status and competitive displacement.

How to interpret the “clinical trials update” for mature CHB drugs

• New trials for legacy agents typically occur as:
  • observational cohort studies
  • resistance/real-world effectiveness analyses
  • retrospective safety reviews
  • combination comparisons that do not restart global phase-3 development
• For HEPSERA, the market reality is usually driven by:
  • guideline repositioning to agents with improved potency and resistance profiles
  • payer and formulary preferences favoring preferred-line therapies

What trial themes dominated HEPSERA historically

• Efficacy in HBeAg-positive and HBeAg-negative CHB
• Resistance evolution under long-term therapy
• Safety tradeoffs, especially renal effects

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Is HEPSERA still being studied for new indications or combinations?

Quick answer: Ongoing development for incremental new indications is not the dominant pattern for HEPSERA; development emphasis in CHB has moved to next-generation nucleotide and interferon-sparing strategies.

Combination and switching trial patterns

Common legacy-drug study designs in CHB include:

• switch from lamivudine-era resistance management to nucleotide therapy
• combination or add-on studies targeting partial responders
• real-world switch studies after virologic breakthrough

Where HEPSERA fits now clinically

• It is most relevant in contexts where:
  • alternative agents are contraindicated
  • prior resistance or resistance history dictates therapy choice
  • cost or access considerations drive payer decisions

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What is the competitive landscape for chronic hepatitis B therapies versus HEPSERA?

Quick answer: HEPSERA faces sustained competition from first-line CHB therapies with higher genetic barrier and improved resistance profiles.

Key competitive drug classes

• Preferred oral agents: high-potency nucleos(t)ide analogs with favorable resistance profiles
• Second-line or special-case options: therapies used when resistance, intolerance, or access constraints occur
• Pegylated interferon approaches: in selected patients based on response likelihood and tolerability

Market share dynamics that displace HEPSERA

• Lower resistance burden increases long-term treatment confidence for prescribers and payers
• Lower monitoring burden can influence formulary placement
• Guideline alignment reduces off-preference use

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How big is the HEPSERA market and who drives demand?

Quick answer: Demand is driven by the remaining CHB patient pool on older regimens, with additional reliance on:

• patients who cannot use preferred agents
• payer coverage for legacy therapies
• ongoing chronic treatment continuity

Demand drivers

• Persistence: CHB therapy is long duration; discontinuation rates are typically lower than in acute indications
• Renal monitoring requirements can deter use, limiting demand growth
• Resistance history can keep some patients on older agents, especially where resistance testing and regimen continuity favor that approach

Geographic market exposure profile

• US/EU sales depend heavily on payer formularies for CHB
• ROW exposure varies by:
  • pricing environment
  • reimbursement structures
  • availability of preferred alternatives

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What is the revenue outlook for HEPSERA through the next 5 years?

Quick answer: The base case is continued erosion versus newer CHB agents, with stabilization only if remaining treatable populations or access constraints keep legacy use from collapsing.

5-year projection logic for HEPSERA (framework)

A defensible projection for a mature CHB product typically hinges on:

• patient share shift from legacy to preferred agents
• net pricing pressure
• generic availability and competitive pricing for the active ingredient class
• clinician switching behavior
• payer formulary tightening

Expected direction of trend

• Base case: steady-to-declining annual revenue
• Downside: accelerated share loss from formulary exclusion or further payer preference shifts
• Upside: niche retention driven by intolerance/contraindication and resistance-history constraints

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When does HEPSERA lose exclusivity and can generics enter?

Quick answer: HEPSERA’s exclusivity era has long ended for the marketed product, and generic competitive pressures limit pricing power.

Why generic entry matters for revenue

• Generic erosion compresses net revenue
• Even without new patent litigation, market pricing typically trends toward active-ingredient benchmarks

Market impact mechanics

• Increased substitution at pharmacy level
• Payer-mandated formulary switching
• Prescriber inertia declines when preferred agents are covered

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What patents protect HEPSERA and how strong is the patent estate?

Quick answer: HEPSERA is a mature molecule with an established IP history; the practical patent landscape typically does not support meaningful exclusivity renewal for the base marketed tablet in the US.

Patent estate categories that historically mattered

• Drug substance and compositions
• Formulation and manufacturing processes
• Method-of-use expansions
• New dosage regimens or combination concepts

Practical conclusion for business planning

• For HEPSERA, the patent estate’s economic impact is usually limited to:
  • narrow formulation/process or method-of-use pockets
  • jurisdiction-specific enforcement windows
• The core product market is dominated by generic availability dynamics

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What is the Orange Book status of HEPSERA?

Quick answer: HEPSERA is not expected to have active, broad US exclusivity that would prevent generic competition for the marketed oral formulation.

Why this drives the commercial outlook

• If the reference product is not protected against approval of AB-rated generics, pricing power is constrained
• Even where narrow patents persist, typical market outcomes trend toward generic substitution

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What patent litigation affects HEPSERA or its generics?

Quick answer: No widely recognized, current US Paragraph IV-driven HEPSERA cycle is expected to be the principal variable for near-term market forecasts.

How litigation would change projections

• A settlement that delays generic entry would support pricing and revenue
• Absent such delays, revenue follows generic pricing and formulary substitution

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What generic entry risks exist for HEPSERA?

Quick answer: Generic substitution risk is structurally present due to the mature status of the molecule and the typical ease of AB-rated approvals once key exclusivity ends.

Key business risks

• price compression from multiple suppliers
• formulary replacement with preferred alternatives
• product stocking shifts at wholesale and IDNs

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How does HEPSERA compare with newer CHB drugs on efficacy and resistance?

Quick answer: Newer nucleos(t)ide analogs generally offer improved resistance profiles and potency, which lowers long-term virologic failure risk versus earlier-generation nucleotide analogs.

Clinical decision impacts

• Higher perceived efficacy drives prescriber preference
• Resistance concerns over longer treatment horizons reduce switching resistance tolerance

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What clinical safety factors influence HEPSERA use today?

Quick answer: Renal monitoring is the main clinical and payer friction point for nucleotide analog use, contributing to reduced adoption versus agents with more favorable long-term safety perceptions.

Risk-management elements

• regular renal function assessment
• dose modification practices if renal impairment appears
• patient selection discipline in real-world settings

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Key Takeaways

• HEPSERA (adefovir dipivoxil) is a mature CHB therapy with no meaningful new development engine visible in the late-stage clinical pipeline.
• Competitive displacement by higher-potency, higher-resistance-barrier CHB agents is the dominant driver of declining or stabilized-with-decline revenue profiles.
• Commercial trajectory is most sensitive to formulary placement, generic substitution dynamics, and continued patient retention among those with intolerance or resistance-history constraints.
• Near-term market outcomes are expected to be pricing- and access-driven more than IP-driven.

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FAQs

1) Does HEPSERA have a current major clinical trial program in CHB?
No dominant recent phase-3 development program is typically associated with HEPSERA, consistent with its mature status and competitive displacement.

2) What is the primary reason clinicians avoid HEPSERA compared with newer CHB agents?
Renal safety monitoring requirements and perceived long-term benefit versus newer, higher-barrier regimens.

3) How does generic availability affect HEPSERA revenue?
Generic substitution typically compresses net pricing and accelerates formulary-driven switching.

4) Which patient subgroups are most likely to remain on HEPSERA?
Patients with contraindications to preferred agents and those where resistance history or access constraints favor continued use.

5) What business levers could change HEPSERA demand in the next few years?
Formulary inclusion/exclusion, payer reimbursement behavior, and local access to preferred CHB alternatives.

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References (APA)

[No cited sources were provided in the prompt.]