CLINICAL TRIALS PROFILE FOR SOFOSBUVIR; VELPATASVIR; VOXILAPREVIR

All Clinical Trials for Sofosbuvir; Velpatasvir; Voxilaprevir

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02185794 ↗	Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Voxilaprevir in Adults With Chronic Hepatitis C Virus Infection	Completed	Gilead Sciences	Phase 1	2014-06-13	The primary objective of the study is to evaluate the safety and tolerability of voxilaprevir (formerly GS-9857) alone or with sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) and antiviral activity of voxilaprevir in adults with genotype 1, 2, 3, 4 hepatitis C virus (HCV) infection. All participants will be monitored for up to 48 weeks after the last dose.
NCT02378935 ↗	Safety and Efficacy of Voxilaprevir Plus Sofosbuvir/Velpatasvir Fixed Dose Combination in Adults With Chronic Genotype 1 HCV Infection	Completed	Gilead Sciences	Phase 2	2015-02-17	This primary objectives of the study are to evaluate the safety, tolerability, and efficacy of voxilaprevir (VOX) plus sofosbuvir/velpatasvir (SOF/VEL) fixed dose combination (FDC) ± ribavirin (RBV) in adults with chronic genotype 1 hepatitis C virus (HCV) infection.
NCT02378961 ↗	Safety and Efficacy of Voxilaprevir Plus Sofosbuvir/Velpatasvir Fixed Dose Combination in Adults With Chronic Non-Genotype 1 HCV Infection	Completed	Gilead Sciences	Phase 2	2015-02-16	The primary objectives of the study are to evaluate the safety, tolerability, and efficacy of voxilaprevir (VOX) plus sofosbuvir/velpatasvir (SOF/VEL) fixed dose combination (FDC) in adults with chronic non genotype 1 hepatitis C virus (HCV) infection.
NCT02533427 ↗	Study to Evaluate Effect of Sofosbuvir/Velpatasvir/GS-9857 Fixed-Dose Combination on the Pharmacokinetics of a Representative Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol	Completed	Gilead Sciences	Phase 1	2015-10-29	This study will evaluate the effect of sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) fixed-dose combination (FDC) + voxilaprevir on the pharmacokinetics (PK) of a representative hormonal contraceptive medication, norgestimate/ethinyl estradiol (Ortho Tri-Cyclen® Lo (OC)) and will assess the effect of norgestimate/ethinyl estradiol on the PK of SOF/VEL/VOX+VOX.
NCT02536313 ↗	Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir Fixed-Dose Combination With or Without Ribavirin in Participants With Chronic Genotype 1 HCV Infection Previously Treated With a Direct Acting Antiviral Regimen	Completed	Gilead Sciences	Phase 2	2015-07-29	The primary objective of this study is to evaluate the efficacy, safety, and tolerability of the treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed dose combination (FDC) ± ribavirin (RBV) in participants with chronic genotype 1 hepatitis C virus (HCV) infection and prior treatment experience with a direct acting antiviral (DAA).
NCT02607735 ↗	Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir in Adults With Chronic HCV Infection Who Have Previously Received Treatment With Direct-Acting Antiviral Therapy	Completed	Gilead Sciences	Phase 3	2015-11-11	The primary objectives of this study are to evaluate the safety and efficacy of treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in adults with chronic hepatitis C virus (HCV) infection who have previously received treatment with direct-acting antiviral therapy. Participants randomized to placebo may be eligible for deferred treatment with active SOF/VEL/VOX.
NCT02607800 ↗	Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir and Sofosbuvir/Velpatasvir in Adults With Chronic HCV Infection Who Have Not Previously Received Treatment With Direct-Acting Antiviral Therapy	Completed	Gilead Sciences	Phase 3	2015-11-16	The primary objectives of this study are to compare the efficacy, safety, and tolerability of treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed dose combination (FDC) for 8 weeks with that of SOF/VEL FDC for 12 weeks in direct-acting antiviral-naive participants with chronic hepatitis C virus (HCV) infection.

Clinical Trial Conditions for Sofosbuvir; Velpatasvir; Voxilaprevir

Condition Name

Condition Name for Sofosbuvir; Velpatasvir; Voxilaprevir
Intervention	Trials
Hepatitis C Virus Infection	9
Hepatitis C	4
Chronic Hepatitis C	2
HIV	1

Condition MeSH

Condition MeSH for Sofosbuvir; Velpatasvir; Voxilaprevir
Intervention	Trials
Hepatitis C	17
Infections	10
Infection	10
Virus Diseases	9

Clinical Trial Locations for Sofosbuvir; Velpatasvir; Voxilaprevir

Trials by Country

Trials by Country for Sofosbuvir; Velpatasvir; Voxilaprevir
Location	Trials
United States	144
Australia	16
Canada	15
New Zealand	10
Puerto Rico	8

Trials by US State

Trials by US State for Sofosbuvir; Velpatasvir; Voxilaprevir
Location	Trials
Texas	8
Tennessee	8
Pennsylvania	8
Florida	8
California	8

Clinical Trial Progress for Sofosbuvir; Velpatasvir; Voxilaprevir

Clinical Trial Phase

Clinical Trial Phase for Sofosbuvir; Velpatasvir; Voxilaprevir
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	6
Phase 2	5

Clinical Trial Status

Clinical Trial Status for Sofosbuvir; Velpatasvir; Voxilaprevir
Clinical Trial Phase	Trials
Completed	13
Recruiting	2
Terminated	1

Clinical Trial Sponsors for Sofosbuvir; Velpatasvir; Voxilaprevir

Sponsor Name

Sponsor Name for Sofosbuvir; Velpatasvir; Voxilaprevir
Sponsor	Trials
Gilead Sciences	13
Helwan University	1
Peking University People's Hospital	1

Sponsor Type

Sponsor Type for Sofosbuvir; Velpatasvir; Voxilaprevir
Sponsor	Trials
Industry	14
Other	7

Sofosbuvir, Velpatasvir, and Voxilaprevir: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction

The combination of sofosbuvir, velpatasvir, and voxilaprevir, marketed as Vosevi, represents a significant advancement in the treatment of chronic hepatitis C virus (HCV) infection. This article delves into the clinical trials that led to its approval, its market impact, and future projections.

Clinical Trials Overview

Trial Design and Participants

The FDA approval of Vosevi was based on evidence from two major clinical trials, POLARIS-1 and POLARIS-4, involving a total of 748 adult patients with chronic HCV infection. These trials included patients who had previously failed treatment with direct-acting antiviral (DAA) drugs, some of whom had cirrhosis and others who did not[1][4].

• POLARIS-1 Trial: This trial was a randomized, multicenter, double-blind, placebo-controlled study comparing Vosevi to a placebo in patients with HCV genotypes 1-6 who had previously failed a regimen containing an NS5A inhibitor.
• POLARIS-4 Trial: This was an open-label trial comparing Vosevi to the combination of sofosbuvir and velpatasvir in patients with HCV genotypes 1 and 3 who had previously failed a sofosbuvir-containing regimen without an NS5A inhibitor[1][4].

Efficacy Outcomes

The primary efficacy outcome in both trials was the sustained virologic response (SVR12), defined as HCV RNA levels below the lower limit of quantification 12 weeks after the completion of treatment.

• SVR12 Rates: In the POLARIS-1 and POLARIS-4 trials, 96% of patients treated with Vosevi achieved SVR12, demonstrating high efficacy across all HCV genotypes, including in patients with compensated cirrhosis[4][5].

Safety Profile

The safety profile of Vosevi was evaluated in these trials, with common adverse events including headache, fatigue, diarrhea, and nausea. The proportion of patients who permanently discontinued treatment due to adverse events was minimal, at 0.2%[4].

Market Analysis

Market Impact

Since its approval in 2017, Vosevi has significantly impacted the HCV treatment market. It is the first once-daily single-tablet regimen approved for salvage therapy in patients who have failed other DAA treatments, addressing a critical unmet need in HCV care[4].

• Patient Reach: Vosevi has expanded the treatment options for patients with HCV, particularly those with genotypes that are harder to treat, such as genotype 4, which is prevalent in sub-Saharan Africa[3].

• Competitive Landscape: Vosevi is part of Gilead’s portfolio of sofosbuvir-based DAA treatments, which have revolutionized HCV treatment. Over 1.4 million patients worldwide have been treated with sofosbuvir-based regimens since 2013[4].

Economic Considerations

The cost-effectiveness of Vosevi is a crucial factor in its market analysis. While the drug is expensive, its high cure rates and the convenience of a single-tablet regimen make it a valuable option for healthcare systems.

• Cost-Benefit Analysis: Studies have shown that treating HCV with effective DAA regimens like Vosevi can reduce long-term healthcare costs by preventing complications such as liver cirrhosis, liver failure, and liver cancer[5].

Projections and Future Outlook

Market Growth

The market for HCV treatments is expected to continue growing as more patients are diagnosed and treated. Vosevi’s unique position as a salvage therapy option is likely to maintain its market share.

• Global Demand: The global demand for HCV treatments is driven by the high prevalence of the disease, especially in regions with limited access to healthcare. Vosevi’s efficacy in treating various genotypes makes it a viable option for these regions[3].

Regulatory and Access Considerations

Regulatory approvals and access programs will play a significant role in Vosevi’s future market performance.

• EMA and FDA Approvals: Vosevi has received approvals from both the FDA and EMA, facilitating its availability in major markets. The EMA granted an accelerated assessment due to its significant therapeutic innovation and public health interest[2][5].

• Access Programs: Gilead has implemented various access programs to make Vosevi more accessible to patients in low-income countries, which is expected to expand its market reach[4].

Safety and Efficacy in Diverse Populations

Real-World Evidence

Real-world studies, such as the one conducted in Rwanda, have further validated the safety and efficacy of Vosevi in diverse populations.

• Rwanda Study: This study evaluated the efficacy and safety of Vosevi in adults with chronic HCV infection, predominantly genotype 4, who had previously failed DAA treatment. The study showed high SVR12 rates and a favorable safety profile, aligning with clinical trial data[3].

Key Takeaways

• High Efficacy: Vosevi has demonstrated high efficacy across all HCV genotypes, including in patients with compensated cirrhosis and those who have failed previous DAA treatments.
• Safety Profile: The drug has a favorable safety profile with common adverse events being mild and transient.
• Market Impact: Vosevi has significantly expanded treatment options for HCV patients, particularly in regions with limited access to healthcare.
• Future Outlook: The market for Vosevi is expected to grow driven by global demand and access programs.

FAQs

What is Vosevi used for?

Vosevi is used for the treatment of adults with chronic hepatitis C virus (HCV) infection, particularly those who have failed previous treatments with direct-acting antiviral (DAA) drugs.

What are the active ingredients in Vosevi?

The active ingredients in Vosevi are sofosbuvir, velpatasvir, and voxilaprevir.

What were the key findings of the POLARIS-1 and POLARIS-4 trials?

The POLARIS-1 and POLARIS-4 trials showed that 96% of patients treated with Vosevi achieved sustained virologic response (SVR12), indicating high efficacy across all HCV genotypes.

What are the common adverse events associated with Vosevi?

The common adverse events associated with Vosevi include headache, fatigue, diarrhea, and nausea.

Is Vosevi available in low-income countries?

Yes, Vosevi is available in low-income countries through various access programs implemented by Gilead.

Sources

1. FDA: Drug Trials Snapshots: VOSEVI - FDA
2. EMA: Vosevi, sofosbuvir/velpatasvir/voxilaprevir - EMA
3. NATAP: Safety and efficacy of sofosbuvir–velpatasvir–voxilaprevir for the treatment of adults in Rwanda with chronic HCV infection
4. Gilead: U.S. Food and Drug Administration Approves Gilead's Vosevi™ (Sofosbuvir/Velpatasvir/Voxilaprevir) for Re-Treatment of Adults with Chronic Hepatitis C Virus
5. EMA: Vosevi | European Medicines Agency (EMA)