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.
NCT02480166 ↗	Comparative Efficacy of Fixed-dose Combination Sofosbuvir + Ledipasvir, 8 vs. 12 Weeks in Chronic Hepatitis C Genotype 6	Completed	Gilead Sciences	Phase 4	2015-06-01	The primary objectives of this study are to describe the efficacy of: 1. 8-week treatment of SOF/LED for treatment-naïve, non-cirrhotic, HCV genotype 6 2. 12-week treatment of SOF/LED for all other HCV-6 populations
NCT02480166 ↗	Comparative Efficacy of Fixed-dose Combination Sofosbuvir + Ledipasvir, 8 vs. 12 Weeks in Chronic Hepatitis C Genotype 6	Completed	Stanford University	Phase 4	2015-06-01	The primary objectives of this study are to describe the efficacy of: 1. 8-week treatment of SOF/LED for treatment-naïve, non-cirrhotic, HCV genotype 6 2. 12-week treatment of SOF/LED for all other HCV-6 populations
NCT02480387 ↗	Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 8 Weeks in Subjects With Chronic Genotype 1 HCV and HIV-1 Co-infection	Completed	Peter J. Ruane, M.D., Inc.	Phase 2	2015-05-01	Target Population: Hepatitis C Treatment Naïve, non-cirrhotic, Chronic genotype 1 hepatitis C virus (HCV) infected adults that are co-infected with human immunodeficiency virus (HIV)-1and have HCV RNA < 6 x106 IU/mL Duration of Subjects will be treated for 8 weeks and followed for 24 weeks post- Treatment: treatment

Clinical Trial Conditions for HARVONI

Condition Name

Condition Name for HARVONI
Intervention	Trials
Hepatitis C	15
Chronic Hepatitis C	4
Hepatitis C, Chronic	3
COVID-19	2

Condition MeSH

Condition MeSH for HARVONI
Intervention	Trials
Hepatitis C	29
Hepatitis	29
Hepatitis A	22
Hepatitis C, Chronic	11

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
Pennsylvania	4
Maryland	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
Unknown status	3
Recruiting	3

Clinical Trial Sponsors for HARVONI

Sponsor Name

Sponsor Name for HARVONI
Sponsor	Trials
Gilead Sciences	12
University of Maryland	3
University of Nebraska	2

Sponsor Type

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

Harvoni (ledipasvir/sofosbuvir) Clinical Trials Update, Market Analysis, and Projection

Last updated: April 27, 2026

What is Harvoni and what is its current clinical footprint?

Harvoni is a fixed-dose combination of ledipasvir (LDV) 90 mg and sofosbuvir (SOF) 400 mg. It is an oral, direct-acting antiviral (DAA) regimen used for chronic hepatitis C virus (HCV) infection across major viral genotypes, with treatment duration and regimen design tailored to baseline factors (e.g., genotype, cirrhosis status, prior treatment history).

Which clinical trials defined Harvoni’s efficacy and safety?

The core efficacy evidence for Harvoni came from Phase 2 and Phase 3 studies that established sustained virologic response (SVR) as the primary endpoint. Key programs:

• ION (Phase 3 program)

  • ION-1, ION-2, ION-3 evaluated LDV/SOF in treatment-naïve and treatment-experienced populations, with or without ribavirin and in compensated cirrhosis subgroups.
  • Endpoints centered on SVR12 (HCV RNA below lower limit of quantification 12 weeks after treatment).

• SIRIUS (Phase 3)

  • Evaluated LDV/SOF in people with compensated cirrhosis and stratified by prior treatment status.

Table 1. Landmark clinical studies used in Harvoni labeling (high-level)

Study	Population focus	Key endpoint
ION-1	Treatment-naïve and previously treated (varied arms)	SVR12
ION-2	Genotype 1 including cirrhosis subsets	SVR12
ION-3	Treatment-naïve, prior treatment history stratification	SVR12
SIRIUS	Compensated cirrhosis	SVR12

Source base: FDA review and clinical pharmacology/clinical efficacy assessment for ledipasvir/sofosbuvir (Harvoni) and ION program summaries. [1–4]

What is the current clinical-trials “update” in practice (post-approval evidence generation)?

After approval, the clinical narrative shifted from pivotal efficacy trials to:

• Real-world effectiveness and outcomes tracking (SVR rates and discontinuation patterns)
• Safety characterization in broader use settings (drug-drug interactions, comorbid populations)
• Label refinements around co-therapies and special populations (e.g., renal impairment classifications, co-infection scenarios)

These updates are typically reflected in label revisions and guideline-adherent practice rather than new Phase 3 registrations. The regulatory record and guideline-aligned use patterns remain the dominant “update” channel for Harvoni.

What is Harvoni’s market basis: approvals, launches, and who sells it?

Harvoni is marketed by Gilead Sciences (U.S. and major territories).

Table 2. Commercial launch posture and regulatory anchor

Market	Regulatory anchor	Status framing
U.S.	FDA approval of ledipasvir/sofosbuvir (Harvoni)	Approved DAA combination
Global	EMA and other national regulators	Standard-of-care backbone in HCV

Source basis: FDA labeling and regulatory summaries for Harvoni. [1–3]

How do payer and guideline dynamics affect Harvoni demand?

Demand has been shaped by:

• The broad adoption of DAAs as first-line therapy for chronic HCV
• Competitive displacement by newer pan-genotypic regimens with simpler dosing/duration or superior tolerability in certain subgroups
• Off-treatment “access” dynamics as health systems move toward streamlined pathways

Harvoni’s commercial profile depends less on new clinical evidence and more on:

• Availability of preferred alternatives
• Territory-level contracting and tender outcomes
• Patient pool size and diagnosis rates (the remaining treatable population after earlier DAA scale-up)

What is the current competitive positioning of Harvoni?

Harvoni belongs to the first wave of DAAs. Its competitive landscape is now dominated by later-generation regimens that reduce regimen complexity across broader patient groups and often shorten the path to treatment.

From a portfolio perspective, Harvoni’s economics typically face:

• Margin pressure due to competitive entry and contracting
• Volume mix changes as newer regimens take share in both treatment-naïve and certain experienced cohorts

Market analysis and projection: what is the likely direction of Harvoni revenue and volume?

Harvoni is already in a mature stage where market size is driven primarily by:

1. Residual diagnosed but untreated HCV population
2. Retreatments and special-pathway patients (where Harvoni remains an option under payer protocols)
3. Country-specific contracting and inventory/channel dynamics

Table 3. Market drivers that control Harvoni trajectory

Driver	Impact mechanism	Net effect for Harvoni (directional)
Residual diagnosed pool	Extends treated volumes after early scaling	Supportive early, then fades
New DAA competition	Replaces preferred regimen in formularies	Downward pressure
Payer contracting/tenders	Forces price concessions and switching	Downward pressure
Guideline simplification	Moves clinicians toward pan-genotypic options	Downward pressure
Retreatment and special subgroups	Creates pockets of continued use	Partial offset

Evidence base for clinical framing: Harvoni dosing and clinical rationale are anchored in labeled indications and DAAs standards. [1–4]

Projection framework (what can be projected from available record)

A projection without explicit internal revenue data or an assigned forecasting model is not reliably supportable. What can be supported from the public regulatory and clinical record is the structural direction:

• Harvoni market outlook is mature and downward-volume trending where newer, simpler regimens displace it.
• Revenue can remain resilient longer than volume in markets where it is entrenched in contracted formularies or where substitution barriers exist (tender cycles, clinical inertia, supply and local pricing).

This direction is consistent with typical DAA lifecycle dynamics: early high-volume scale after approval, followed by share erosion as competition expands.

What endpoints and safety considerations matter for ongoing clinical relevance?

Even in mature markets, Harvoni’s clinical relevance remains tied to:

• SVR12 achievement durability as the core efficacy benchmark
• Tolerability and discontinuation rates
• Drug-drug interaction handling (especially in patients with comorbidities)

Label-based information anchors these considerations. [1–3]

Key label-relevant clinical considerations (high-level)

Harvoni labeling contains:

• Treatment duration selection based on genotype, cirrhosis status, and prior treatment history
• Specific dosing directions and monitoring considerations
• Interaction guidance for co-administered medicines

These are the practical mechanisms by which real-world clinicians decide Harvoni use, not newly emerging trial endpoints. [1–3]

Is Harvoni used for genotype-specific or pan-genotypic practice today?

Harvoni is not a pan-genotypic regimen in the way later combinations are. Its use pattern reflects:

• Label-supported genotype coverage
• Payer preferences that prioritize pan-genotypic regimens where possible

This contributes to ongoing substitution pressure and is consistent with competitive shift in HCV therapeutics.

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Key Takeaways

• Harvoni (ledipasvir/sofosbuvir) is an oral DAA regimen whose pivotal clinical evidence came from the ION Phase 3 program and related studies such as SIRIUS, with SVR12 as the key endpoint. [1–4]
• The post-approval “clinical trials update” is dominated by real-world effectiveness and safety characterization rather than new pivotal registrations. Practical updates are reflected in label content and guideline-aligned use. [1–3]
• Commercially, Harvoni is in a mature market stage where competitive displacement and payer contracting drive long-term decline in share and often volume, offset only by residual diagnosed patient pools and special-use pockets. [1–3]
• Reliable forward-looking revenue forecasting requires internal or third-party market sizing inputs not present in the regulatory and trial record alone; directionally, share erosion is structurally consistent with mature DAA lifecycle patterns.

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FAQs

1) What clinical endpoint defined Harvoni efficacy in pivotal trials?

SVR12, measured as undetectable HCV RNA 12 weeks after treatment completion. [1–4]

2) Which Phase 3 program is most associated with Harvoni’s approval evidence?

The ION Phase 3 program (ION-1, ION-2, ION-3) supporting ledipasvir/sofosbuvir efficacy across labeled populations. [1–4]

3) Who markets Harvoni?

Gilead Sciences. [1–3]

4) Why does Harvoni face pricing and volume pressure today?

Because payer formularies shift toward newer DAAs, often pan-genotypic or simpler regimens, and contracting drives price concessions and regimen switching. [1–3]

5) Does Harvoni’s current use depend on newly emerging trials?

No. Routine clinical use is primarily governed by label directions, guideline protocols, and drug-drug interaction management rather than ongoing pivotal trial results. [1–3]

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References (APA)

[1] FDA. (2014). Harvoni (ledipasvir and sofosbuvir) prescribing information. U.S. Food and Drug Administration.
[2] FDA. (2015). Medical review(s) and pharmacology/toxicology review for ledipasvir/sofosbuvir (Harvoni). U.S. Food and Drug Administration.
[3] European Medicines Agency (EMA). (Various dates). Harvoni assessment history and EPAR. European Medicines Agency.
[4] FDA. (2016). Clinical review/labeling documentation supporting the efficacy and safety of ledipasvir/sofosbuvir (Harvoni). U.S. Food and Drug Administration.