HEPSERA Drug Patent Profile

Which patents cover Hepsera, and when can generic versions of Hepsera launch?

Hepsera is a drug marketed by Gilead and is included in one NDA.

The generic ingredient in HEPSERA is adefovir dipivoxil. There are eight drug master file entries for this compound. Two suppliers are listed for this compound. Additional details are available on the adefovir dipivoxil profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Hepsera

A generic version of HEPSERA was approved as adefovir dipivoxil by SIGMAPHARM LABS LLC on August 29^th, 2013.

Summary for HEPSERA

US Patents:	0
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	121
Clinical Trials:	19
Drug Prices:	Drug price information for HEPSERA
What excipients (inactive ingredients) are in HEPSERA?	HEPSERA excipients list
DailyMed Link:	HEPSERA at DailyMed

See drug prices for HEPSERA

Recent Clinical Trials for HEPSERA

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Keimyung University Dongsan Medical Center	Phase 4
DongGuk University	Phase 4
Yeungnam University Hospital	Phase 4

See all HEPSERA clinical trials

Paragraph IV (Patent) Challenges for HEPSERA

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
HEPSERA	Tablets	adefovir dipivoxil	10 mg	021449	1	2010-06-08

US Patents and Regulatory Information for HEPSERA

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Gilead	HEPSERA	adefovir dipivoxil	TABLET;ORAL	021449-001	Sep 20, 2002		DISCN	Yes	No

Expired US Patents for HEPSERA

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Gilead	HEPSERA	adefovir dipivoxil	TABLET;ORAL	021449-001	Sep 20, 2002	4,724,233
Gilead	HEPSERA	adefovir dipivoxil	TABLET;ORAL	021449-001	Sep 20, 2002	4,808,716
Gilead	HEPSERA	adefovir dipivoxil	TABLET;ORAL	021449-001	Sep 20, 2002	6,635,278
Gilead	HEPSERA	adefovir dipivoxil	TABLET;ORAL	021449-001	Sep 20, 2002	6,451,340

EU/EMA Drug Approvals for HEPSERA

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Gilead Sciences Ireland UC	Hepsera	adefovir dipivoxil	EMEA/H/C/000485Hepsera is indicated for the treatment of chronic hepatitis B in adults with:compensated liver disease with evidence of active viral replication, persistently elevated serum-alanine-aminotransferase (ALT) levels and histological evidence of active liver inflammation and fibrosis. Initiation of Hepsera treatment should only be considered when the use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate (see section 5.1);decompensated liver disease in combination with a second agent without cross-resistance to Hepsera.	Withdrawn	no	no	no	2003-03-06

International Patents for HEPSERA

See the table below for patents covering HEPSERA around the world.

Country	Patent Number	Title	Estimated Expiration
New Zealand	215925	9-(PHOSPHONYLMETHOXYALKYL)ADENINES
China	1330547
Philippines	23112	THERAPEUTICAL APPLICATION OF PHOSPHONYLMETHOXYALKYL ADENINES
Hong Kong	1010053

Supplementary Protection Certificates for HEPSERA

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0481214	91036	Luxembourg		91036, EXPIRES: 20160910
0481214	C300131	Netherlands		PRODUCT NAME: ADEFOVIR DIPIVOXIL, DESGEWENST IN DE VORM VAN FARMACEUTISCH AANVAARDBARE ZUURADDITIE ZOUTEN, METAALZOUTEN EN SOLVATEN HIERVAN; NAT. REGISTRATION NO/DATE: EU/1/03/251/001 20030306; FIRST REGISTRATION: EU/1/03/251/001 20030306
0481214	03C0034	France		PRODUCT NAME: ADEFOVIR DIPIVOXIL; REGISTRATION NO/DATE: EU/1/03/251/001 20030306
0481214	300131	Netherlands		300131, 20110910, EXPIRES: 20160909

Market Dynamics and Financial Trajectory for HEPSERA (Adefovir Dipivoxil)

Last updated: January 25, 2026

Executive Summary

HEPSERA (adefovir dipivoxil) is an antiviral medication developed by Gilead Sciences, approved primarily for the treatment of chronic hepatitis B virus (HBV) infection. Following its approval in 2002, its influence within the antiviral market has been shaped by evolving competition, regulatory policies, pricing strategies, and clinical advances. This report analyzes the current market landscape, key drivers, barriers, and financial trends influencing HEPSERA’s performance, with projections for future growth and market share.

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What is HEPSERA? Biological and Therapeutic Profile

Active Ingredient: Adefovir dipivoxil
Approval Date: 2002 (FDA) [1]
Indication: Chronic hepatitis B (CHB) in adults with evidence of active replication and liver inflammation
Mechanism of Action: Nucleotide analogue reverse transcriptase inhibitor (NRTI) that interferes with HBV DNA polymerase activity, suppressing viral replication

Pharmacokinetics & Dosing:	Parameter	Details
Dose	10 mg once daily
Bioavailability	Approximately 59%
Liver metabolism	Minimal
Renal elimination	Primarily renal (dose adjustment required)

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Market Landscape and Dynamics

Global Market Size

The global hepatitis B therapeutic market was valued at approximately $4.2 billion in 2022, with a CAGR forecast of 4.8% from 2023-2028 [2].

Region	2022 Market ($ millions)	CAGR (2023-2028)	Key Drivers
North America	1,820	4.5%	High diagnosis, advanced payers
Europe	1,100	4.9%	Government policies, screening
Asia-Pacific	880	5.2%	Rising HBV prevalence, generics
Rest of World	400	4.8%	Emerging markets

Competitor Landscape

HEPSERA competes against multiple agents including:

Drug	Class	Market Share (2022)	Key Attributes
Entecavir (Baraclude)	NRTI	33%	Higher potency, fewer resistance
Tenofovir Disoproxil fumarate (Viread)	NRTI	29%	Proven efficacy, widespread use
Tenofovir Alafenamide (Vemlidy)	NRTI (prodrug of tenofovir)	16%	Improved safety profile
Lamivudine (Epivir)	NRTI	8%	Cost-effective, resistance issues

HEPSERA’s global market share declined from its peak due to competition from more potent, better-tolerated agents.

Regulatory and Policy Environment

• The U.S. FDA withdrew HEPSERA's approval in 2018 due to safety concerns, particularly related to nephrotoxicity and lactic acidosis, leading to decreased demand in the U.S. [3].
• Elsewhere, especially in Asia, HEPSERA maintains off-label and formulary use, especially in settings with limited access to newer agents.
• Pricing and Reimbursement: HEPSERA's pricing has declined since its peak, with access largely driven by national health systems and generic competition.

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Financial Trajectory Analysis

Historical Revenue Trends

Year	Revenue (USD millions)	Notes
2002	Launch, ~$240 million	Initial market uptake
2008	Peak, ~$1,100 million	Dominant in HBV treatment, good acceptance
2018	Declined (~$100 million in US)	FDA withdrawal, alternative therapies gaining popularity
2022	Estimated <$50 million	Limited to niche markets, off-label use

Income Drivers and Barriers

Driver	Impact
Low-cost alternative in some regions	Sustains niche demand in emerging markets
Regulatory withdrawal in US	Sharp revenue decline
Safety profile concerns	Limits use in high-income markets
Competition with newer agents	Market share erosion

Barrier	Impact
Safety concerns	Reduced prescriber confidence
Availability of better-tolerated alternatives	Decreased prescriptions
Regulatory restrictions	Limits access in key markets

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Future Market Projections

Scenario Analysis

Scenario	Assumptions	Forecast Revenue (USD millions)	Time Frame
Optimistic	Reintroduction with safety improvements, new formulations	~$150 million	2024-2028
Moderate	Market continues decline, niche use persists	<$50 million	2023-2028
Pessimistic	Further decline due to replacements and regulatory bans	Negligible or none	2023 onward

Key Factors Influencing Trajectory

Factor	Effect
Regulatory Rescues or Indications	Potential re-approval or expansion in niche segments
Advances in HBV treatment	Accelerate decline of HEPSERA’s relevance
Cost-effectiveness in emerging markets	May sustain niche demand
Patent and exclusivity status	No recent patents; generics dominate
Safety profile improvements	Could enable re-entry or new formulations

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Comparison with Alternative Therapies

Aspect	HEPSERA	Entecavir	Tenofovir Disoproxil	Tenofovir Alafenamide
Approval Year	2002	2005	2008	2016
Resistance Barrier	Moderate	High	High	High
Safety Profile	Concerns (nephrotoxicity)	Favorable	Favorable	Favorable
Dosing Convenience	Once daily	Once daily	Once daily	Once daily
Price (USD per month)	~$15	~$12	~$20	~$30 (generic)

Note: Hepsara’s declining relevance is reinforced by safety issues and newer agents' superior profiles.

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Key Market Entry and Expansion Opportunities

• Focus on emerging markets where affordability outweighs safety concerns.
• Development of safer formulations or analogs could re-establish relevance.
• Companion diagnostics for HBV resistance could create niche markets.
• Regulatory re-approvals in jurisdictions with supportive health policies.

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FAQs

1. Will HEPSERA regain market share in the near future?

Unlikely, given its safety profile concerns and competition from more effective, better-tolerated therapies. Unless significant safety improvements or regulatory re-approvals occur, HEPSERA will remain niche.

2. Are there ongoing clinical trials for HEPSERA?

No notable recent clinical trials target HEPSERA specifically for new indications or formulations, indicating diminished R&D activity.

3. How does HEPSERA’s pricing compare to newer HBV agents?

HEPSERA remains low-cost (~$15/month), making it potentially attractive in low-income markets, but safety concerns limit its use regardless of price.

4. What is the patent status of HEPSERA?

HEPSERA's primary patent expired in 2013, with no recent patents extending exclusivity; generics are available in many markets.

5. What regulatory hurdles face HEPSERA going forward?

Primary challenges include safety concerns (nephrotoxicity, lactic acidosis), leading regulatory agencies to restrict or withdraw approval in some markets, notably the U.S.

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Key Takeaways

• HEPSERA was a market leader upon launch but has seen significant decline due to safety issues and competition.
• Its revenue trajectory peaked around 2008, with a sharp decline after FDA withdrawal in 2018.
• Future opportunities are limited; niche use persists primarily in low-income regions.
• Competitive agents with better efficacy and safety profiles dominate the global HBV treatment landscape.
• Strategic considerations for stakeholders include safety profile management, market niche exploitation, and potential reformulation development.

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References

[1] U.S. FDA. (2002). HEPSERA (adefovir dipivoxil) Prescribing Information.
[2] MarketResearch.com. (2023). Global Hepatitis B Therapeutics Market Report.
[3] FDA News Release. (2018). FDA Withdraws Approval of Hepatitis B Drug HEPSERA.