CLINICAL TRIALS PROFILE FOR HARVONI

All Clinical Trials for HARVONI

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02339038 ↗	Community-based Treatment of Chronic Hepatitis C Monoinfection and Coinfection With HIV in the District of Columbia	Completed	National Institutes of Health Clinical Center (CC)	Phase 4	2015-01-07	Background: - Treatment for Hepatitis C has changed a lot in the past 2 years. Most of this change comes from a combination of medicines that is yielding high cure rates. But its long-term effects are uncertain. One problem is that a lot of people need the treatment, but only a few specialists can give it. The success rate for Hepatitis C treatment by primary care doctors, nurse practitioners, or physician assistants is largely unknown. Researchers want to see how provider type affects treatment outcomes. They will conduct a large, community-based study in the District of Columbia. Objectives: - To see if people can be treated for Hepatitis C safely and successfully in community-based health centers. Eligibility: - Adults who need treatment for chronic Hepatitis C infection. Design: - Participants will be screened with blood tests. Their current medicines will be reviewed. - Participants will give researchers access to their medical records. Researchers will follow participants through these records. - Participants will see a primary care or infectious disease provider. The provider will tell them about their treatment. They will be told how often they will visit the provider and how often they will have their blood drawn. They will get a calendar of study visits. - Participants will take Harvoni for 8, 12, or 24 weeks. They will visit their care provider monthly. - Participants will have monthly follow-up visits for up to 3 months after they finish their medicine. - Participants will have yearly follow-up visits with their care provider for up to 10 years.
NCT02347345 ↗	Immunologic Effects of HCV Therapy With HARVONI in HCV Genotype 1 Chronically Mono-infected Active and Former IDUs	Completed	National Institute on Drug Abuse (NIDA)	Phase 4	2016-11-15	The investigator's hypothesis is that active injectors will show a partial reduction in markers of immune activation with HCV therapy whereas non-injectors will show a more significant reduction in these markers, and will exhibit levels of immune activation that approach that seen in similarly studied healthy volunteers.This is based on observations that this group of investigators have made. They have shown that individuals who inject drugs have high level of immune activation in blood and tissue. Immune activation or chronic inflammation has been associated with accelerated aging, cardiovascular, renal and liver disease as well as CNS dysfunction. It remains unclear whether increased levels of immune activation are due to non-sterile injection of drugs, chronic infection with Hepatitis C, chronic opiate use, or perhaps combinations of all 3. To understand the potential contribution of infection with Hepatitis C the investigators will compare levels of immune activation pre- and post treatment with an all oral, one pill once daily, interferon sparing treatment of HCV in 2 groups of chronically HCV infected patients- one actively injecting with drugs and the other free of injection for at least 4 months. Immune activation comparisons will also include non-injecting healthy volunteers.
NCT02347345 ↗	Immunologic Effects of HCV Therapy With HARVONI in HCV Genotype 1 Chronically Mono-infected Active and Former IDUs	Completed	Rockefeller University	Phase 4	2016-11-15	The investigator's hypothesis is that active injectors will show a partial reduction in markers of immune activation with HCV therapy whereas non-injectors will show a more significant reduction in these markers, and will exhibit levels of immune activation that approach that seen in similarly studied healthy volunteers.This is based on observations that this group of investigators have made. They have shown that individuals who inject drugs have high level of immune activation in blood and tissue. Immune activation or chronic inflammation has been associated with accelerated aging, cardiovascular, renal and liver disease as well as CNS dysfunction. It remains unclear whether increased levels of immune activation are due to non-sterile injection of drugs, chronic infection with Hepatitis C, chronic opiate use, or perhaps combinations of all 3. To understand the potential contribution of infection with Hepatitis C the investigators will compare levels of immune activation pre- and post treatment with an all oral, one pill once daily, interferon sparing treatment of HCV in 2 groups of chronically HCV infected patients- one actively injecting with drugs and the other free of injection for at least 4 months. Immune activation comparisons will also include non-injecting healthy volunteers.

Clinical Trial Conditions for HARVONI

Condition Name

Condition Name for HARVONI
Intervention	Trials
Hepatitis C	15
Chronic Hepatitis C	4
Hepatitis C, Chronic	3

Condition MeSH

Condition MeSH for HARVONI
Intervention	Trials
Hepatitis C	29
Hepatitis	29
Hepatitis A	22

Clinical Trial Locations for HARVONI

Trials by Country

Trials by Country for HARVONI
Location	Trials
United States	62
Italy	6
Egypt	5
Canada	3
Korea, Republic of	2

Trials by US State

Trials by US State for HARVONI
Location	Trials
New York	8
California	7
Texas	5
District of Columbia	4
Pennsylvania	4

Clinical Trial Progress for HARVONI

Clinical Trial Phase

Clinical Trial Phase for HARVONI
Clinical Trial Phase	Trials
Phase 4	16
Phase 3	3
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for HARVONI
Clinical Trial Phase	Trials
Completed	21
Active, not recruiting	3
Terminated	3

Clinical Trial Sponsors for HARVONI

Sponsor Name

Sponsor Name for HARVONI
Sponsor	Trials
Gilead Sciences	12
University of Maryland	3
National Institutes of Health Clinical Center (CC)	2

Sponsor Type

Sponsor Type for HARVONI
Sponsor	Trials
Other	59
Industry	17
NIH	7

Clinical Trials Update, Market Analysis, and Projection for Harvoni

Last updated: October 28, 2025

Introduction

Harvoni (ledipasvir/sofosbuvir) revolutionized hepatitis C virus (HCV) treatment upon its U.S. Food and Drug Administration (FDA) approval in 2014. As a direct-acting antiviral (DAA), it offers a high cure rate with a simplified, once-daily oral regimen, reducing treatment durations to 8-12 weeks. This article examines recent clinical trial developments, current market dynamics, and future projections for Harvoni, highlighting its strategic positioning within the evolving hepatitis C therapeutics landscape.

Clinical Trials Update

Recent Clinical Advancements

While Harvoni's initial approval marked a breakthrough, ongoing clinical studies continue to explore its extended applications:

• Treatment in Special Populations: Several Phase IV real-world evidence studies have reinforced Harvoni's efficacy in populations historically difficult to treat, including patients with cirrhosis, co-infections (HIV/HCV), and transplant recipients. For example, the ASTRAL trials primarily showcased impressive sustained virologic response (SVR) rates exceeding 95% across diverse cohorts (ASTRAL-1, -2, -3)[1].

• Lengthening and Shortening Treatment Durations: Recent trials investigate optimized regimens, with some demonstrating successful SVR at 8-week courses in non-cirrhotic patients, potentially reducing costs and improving adherence.

• Re-treatment Strategies: Data from real-world studies show Harvoni effectively re-treats patients who failed prior DAA therapies, including those previously treated with protease inhibitors.

• Combination with Other Agents: Although Harvoni is a standalone regimen, ongoing trials assess its combination with novel agents to broaden therapeutic scope, especially for resistant HCV strains.

Safety and Resistance Profiles

• Long-term Safety: Post-marketing surveillance confirms Harvoni's well-tolerated profile, with adverse events (AEs) primarily mild and transient. Common AEs include headache, fatigue, and nausea.

• Resistance Concerns: Limited resistance development has been observed, mainly associated with baseline NS5A resistance-associated polymorphisms. Resistance testing guides treatment, and no significant resistance-related setbacks have been reported recently.

Regulatory and Market Approvals

• Extended Indications: The FDA has approved Harvoni for pediatric patients aged 12-17 with chronic HCV genotype 1, expanding its clinical utility.

• Global Approvals: Harvoni is approved in over 100 countries, including EU member states, with ongoing negotiations to expand access in low-income regions, leveraging generic manufacturing.

Market Analysis

Historical Market Performance

Harvoni swiftly dominated the HCV treatment market post-launch, capturing approximately 60-70% of the market share in the United States by 2016. Its high efficacy, simplified regimen, and reduced treatment duration led to rapid adoption by healthcare providers.

Competitive Landscape

• Direct Competition: Gilead's own subsequent formulations (e.g., Epclusa, Vosevi) and AbbVie's Mavyret challenged Harvoni's dominance by offering pan-genotypic coverage and shorter courses.

• Pricing and Accessibility: Initially priced at approximately $94,500 for a 12-week course, rebates, negotiations, and emerging generics have driven prices downward, improving access and adherence.

• Market Transition: The shift from specialized antiviral regimens to broad-spectrum, pan-genotypic therapies leads to a gradual decline in Harvoni sales, especially in markets where these alternatives are preferred.

Current Market Dynamics

• Sales Trends: After peaking at over $4.5 billion globally in 2015, sales have declined by roughly 30-40% annually since 2019, correlating with market saturation and competitive offerings.

• Geographical Variations: High-income markets (US, Europe) saw faster sales declines, whereas low- and middle-income regions exhibit increasing adoption, supported by generic manufacturing and government subsidy programs.

Key Challenges

• Pricing Pressure: Payers and governments continue to negotiate discounts, impacting profit margins.

• Patent Expirations and Generics: Patent expiration in key markets is anticipated within the next 2-5 years, opening markets for biosimilars and generic versions, which could further erode branded sales.

Market Projection and Future Outlook

Forecasting Methodology

Analyzing current trends, competitive landscape reports, and pipeline developments, market analysts project a continued decline in Harvoni's revenue in advanced markets over the next five years, with some stabilization in emerging regions.

Revenue Projections (2023-2028)

• Global Sales: Estimated to decrease to approximately $1.2 billion by 2028, down from peak sales.

• Market Share: Harvoni's share within Gilead's HCV portfolio will likely diminish as newer, pan-genotypic, and ribavirin-free regimens gain favor.

• Potential Resurgence: Breakthroughs in combination therapies and expanding indications in pediatric and special populations might sustain residual demand.

Strategic Implications

• Pipeline Integration: Gilead is focusing on developing pan-genotypic regimes (e.g., Epclusa, Vosevi) with broader influence over the HCV market.

• Brand Lifecycle Management: Continued optimization of manufacturing, negotiation of pricing, and potential repurposing of Harvoni for resistant or complex cases could prolong its market presence.

• Global Access: Leveraging generic manufacturing to expand access in underserved markets presents a growth avenue despite declining branded sales.

Conclusion

Harvoni's clinical success transformed hepatitis C management, setting new standards for cure rates and treatment simplicity. While its clinical profile remains robust, market dynamics driven by generic competition, evolving treatment paradigms, and patent expirations forecast a gradual decline in revenue. Strategic repositioning within the Gilead portfolio and expanding access globally ensure that Harvoni retains clinical relevance, albeit with diminishing commercial prominence.

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Key Takeaways

• Clinical Efficacy Remains High: Harvoni consistently delivers SVR rates above 95%, including in difficult-to-treat populations, supported by extensive real-world data.

• Market Decline Predicted: Revenue declines are expected due to patent expirations, generic competition, and the rise of pan-genotypic, shorter regimens.

• Global Access Tie-ins: Expanding production of generics, particularly in low-income markets, offers growth potential despite declining brand sales.

• Pipeline and Combinations: Future applications may include treatment of resistant strains, pediatric populations, and combination regimens to sustain relevance.

• Strategic Focus Needed: Gilead’s emphasis on pan-genotypic therapies and market diversification will determine Harvoni’s long-term footprint.

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FAQs

1. What are the main limitations of Harvoni's current market position?
Market saturation, patent expiration, and competition from pan-genotypic and cost-effective generics are primary limitations impinging on Harvoni's market share.

2. Are there ongoing trials to expand Harvoni’s indications?
While no major new trials are focused on Harvoni itself, research continues into optimizing treatment durations and combining with other agents for special populations, which could indirectly influence its use.

3. How has pricing affected Harvoni’s global reach?
High initial pricing restricted access in lower-income countries; however, generic manufacturing and negotiated discounts have improved affordability and distribution.

4. What role does resistance play in Harvoni’s treatment landscape?
Resistance-associated polymorphisms are relatively uncommon but can impact retreatment success, emphasizing the need for resistance testing in certain cases.

5. Could Harvoni regain market dominance?
Unlikely, given the current trajectory toward pan-genotypic regimens; however, it remains a vital option for specific patient subsets and resistant cases.

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Sources:
[1] Gilead Sciences. ASTRAL Clinical Trial Program. Accessed 2023.