CLINICAL TRIALS PROFILE FOR EPCLUSA

505(b)(2) Clinical Trials for Epclusa

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
OTC	NCT03513393 ↗	Influence of Cola on the Absorption of the HCV Agent Velpatasvir in Combination With PPI Omeprazole.	Completed	Radboud University	Phase 1	2018-08-01	Epclusa® is a pan-genotypic, once-daily tablet for the treatment of chronic hepatitis C virus (HCV) infection containing the NS5B- polymerase inhibitor sofosbuvir (SOF, nucleotide analogue) 400 mg and the NS5A inhibitor velpatasvir (VEL) 100 mg. Velpatasvir has pH dependent absorption. At higher pH the solubility of velpatasvir decreases. It has been shown that in subjects treated with proton pump inhibitors (PPIs) such as omeprazole, the absorption of velpatasvir is reduced by 26-56%, depending on the dose of omeprazole, concomitant food intake, and timing/sequence of velpatasvir vs. omeprazole intake. As a result, concomitant intake of PPIs with velpatasvir is not recommended. For a number of reasons, the prohibition of PPI use with velpatasvir is a clinically relevant problem. First, PPI use is highly frequent in the HCV-infected subject population with prevalences reported up to 40%. Second, PPIs are available as over-the-counter medications and thus can be used by subjects without informing their physician. Third, although HCV therapy is generally well tolerated, gastro-intestinal symptoms such as abdominal pain and nausea are frequently reported, which my lead to PPI use. One solution of this problem could be the use of other acid-reducing agents such as H2-receptor antagonists or antacids. In general, they have a less pronounced effect on intragastric pH, and are considered less effective than PPIs by many patients and physicians. A second solution would be the choice of another HCV agent or combination that is not dependent on low gastric pH for its absorption such as daclatasvir. Daclatasvir, however, is not a pan-genotypic HCV agent and may be less effective against GT 2 and 3 infections than velpatasvir. Second, not all subjects have access to daclatasvir, depending on health insurance company or region where they live. A third solution, and the focus of this COPA study, is to add a glass of the acidic beverage cola at the time of velpatasvir administration in subjects concurrently treated with PPIs. This intervention has been shown to be effective for a number of drugs from other therapeutic classes who all have in common a reduced solubility (and thus reduced absorption) at higher intragastric pH, namely erlotinib, itraconazole, ketoconazole. The advantages of this approach are: (1) only a temporary decrease in gastric pH at the time of cola intake; the rest of the day the PPI will have its therapeutic effect (2) cola is available worldwide (3) the administration of cola can be done irrespective to the timing of PPI use.

All Clinical Trials for Epclusa

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02300103 ↗	Efficacy And Safety Of Sofosbuvir/Velpatasvir Fixed Dose Combination With Ribavirin in Chronic HCV Infected Adults Who Participated in a Prior Gilead Sponsored HCV Treatment Study	Completed	Gilead Sciences	Phase 2	2014-12-01	The primary objective of this study is to evaluate the efficacy, safety and tolerability of treatment with sofosbuvir/velpatasvir (Epclusa®; SOF/VEL) with ribavirin (RBV) for 24 weeks in adults with chronic hepatitis C virus (HCV) infection who participated in a prior Gilead sponsored study and did not achieve sustained virologic response (SVR).
NCT02639247 ↗	Safety and Efficacy of SOF/VEL/VOX FDC for 12 Weeks and SOF/VEL for 12 Weeks in DAA-Experienced Adults With Chronic HCV Infection Who Have Not Received an NS5A Inhibitor	Completed	Gilead Sciences	Phase 3	2015-12-23	The primary objectives of the study are to evaluate the efficacy, safety, and tolerability of treatment with sofosbuvir/velpatasvir/voxilaprevir (Vosevi®; SOF/VEL/VOX) fixed-dose combination (FDC) for 12 weeks and of sofosbuvir/velpatasvir (Epclusa®; SOF/VEL) FDC for 12 weeks in direct-acting antiviral (DAA)-experienced adults with chronic hepatitis C virus (HCV) infection with or without cirrhosis who have not received prior treatment with a regimen containing an inhibitor of the HCV NS5A protein.
NCT02743897 ↗	Transplanting Hepatitis C Kidneys Into Negative Kidney Recipients	Active, not recruiting	Merck Sharp & Dohme Corp.	Phase 1/Phase 2	2016-05-01	This study is being conducted to determine safety and effectiveness of transplanting kidneys from Hepatitis C-positive donors into Hepatitis C-negative patients on the kidney transplant waitlist, who will then be treated with the appropriate direct-acting antiviral (DAA) after the single kidney transplantation.

Clinical Trial Conditions for Epclusa

Condition Name

Condition Name for Epclusa
Intervention	Trials
Hepatitis C	21
Hepatitis C, Chronic	10
COVID-19	2

Condition MeSH

Condition MeSH for Epclusa
Intervention	Trials
Hepatitis C	37
Hepatitis	29
Hepatitis A	19

Clinical Trial Locations for Epclusa

Trials by Country

Trials by Country for Epclusa
Location	Trials
United States	85
Australia	7
Italy	6
Canada	5
Brazil	3

Trials by US State

Trials by US State for Epclusa
Location	Trials
Pennsylvania	13
Massachusetts	8
Maryland	7
New York	6
California	5

Clinical Trial Progress for Epclusa

Clinical Trial Phase

Clinical Trial Phase for Epclusa
Clinical Trial Phase	Trials
Phase 4	17
Phase 3	3
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for Epclusa
Clinical Trial Phase	Trials
Recruiting	10
Completed	10
Active, not recruiting	9

Clinical Trial Sponsors for Epclusa

Sponsor Name

Sponsor Name for Epclusa
Sponsor	Trials
Gilead Sciences	13
University of Pennsylvania	3
Radboud University	2

Sponsor Type

Sponsor Type for Epclusa
Sponsor	Trials
Other	52
Industry	16
NIH	4

Clinical Trials and Efficacy of Epclusa

Overview of Epclusa

Epclusa, a fixed-dose combination of sofosbuvir and velpatasvir, has been a groundbreaking treatment for chronic hepatitis C virus (HCV) infection. Here’s a detailed look at its clinical trials, efficacy, and market analysis.

Clinical Trials

Adult Population

The approval of Epclusa for adults was based on several clinical trials, including the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies. These trials demonstrated high sustained virologic response rates (SVR12) across all HCV genotypes. The overall SVR12 rate was 98% (1,015/1,035) across the three pooled studies, indicating a high cure rate for HCV infection without cirrhosis or with compensated cirrhosis[3].

Pediatric Population

For children, Epclusa has undergone multiple clinical trials to expand its indication. A Phase 2, open-label clinical trial (Study 1143) involving 175 children aged 6 and older showed high SVR12 rates: 93% for genotype 1, and 100% for genotypes 2, 3, 4, and 6 in the 12- to <18-year-old group. For children aged 6 to <12 years, the SVR rates were 93% for genotype 1, 91% for genotype 3, and 100% for genotypes 2 and 4[1].

A newer formulation of Epclusa, an oral pellet, was approved for children as young as 3 years old. This Phase 2 trial enrolled 41 children and achieved an SVR12 rate of 83% (34/41) among all patients, with specific genotype results showing 88% for genotype 1, 50% for genotype 2, and 100% for genotypes 3 and 4[4].

Safety Profile

The safety profile of Epclusa has been consistent across various clinical trials. In adults, the most common adverse reactions were headache and fatigue, with a safety profile similar to placebo treatment. In children, the safety profile was generally consistent with that observed in adults, although vomiting and product use issues were noted in younger children[1][3][4].

Market Analysis

Market Share and Revenue

Epclusa has maintained a significant market share in the HCV treatment market. As of the first half of 2024, Epclusa held approximately 56% of the new prescription (NRx) market share in the US, with Mavyret, another HCV treatment, holding around 41%[2].

The total US HCV market net revenues for Epclusa and Mavyret were substantial, with Epclusa generating $826 million in the first half of 2024. The net revenue per patient treated with Epclusa was $17,611, indicating a high-value market segment[2].

Market Drivers and Challenges

The HCV market is driven by several factors, including US government initiatives, optimal product profiles, and the removal of prescribing barriers by payors. However, challenges persist, such as the need for better adherence among high-risk populations, including those with substance abuse disorders[2].

Market Projections

Potential Market Value

The US HCV market is projected to remain stable, with a potential market value exceeding $20 billion. The treatment of all currently chronically infected HCV patients in the US could generate significant revenue, estimated at around $1.5 billion annually[2].

Future Developments

Gilead Sciences continues to invest in HCV research and development. The approval of new formulations, such as the oral pellet for younger children, and ongoing clinical trials for other HCV treatments, indicate a commitment to expanding treatment options and improving patient outcomes[4].

Competitive Landscape

Epclusa competes primarily with Mavyret, another pangenotypic HCV treatment. While Mavyret has a shorter treatment duration and includes a protease inhibitor, it interacts with many drugs and must be taken with food. Epclusa, on the other hand, does not interact with many drugs and can be taken with or without food, although it has a longer treatment duration[2].

Key Takeaways

• High Efficacy: Epclusa has demonstrated high SVR12 rates across all HCV genotypes in both adult and pediatric populations.
• Safety Profile: The safety profile of Epclusa is generally consistent with that of placebo treatment, with common adverse reactions being headache and fatigue.
• Market Dominance: Epclusa holds a significant market share in the US HCV treatment market.
• Future Prospects: The US HCV market is projected to remain valuable, with ongoing developments in treatment options and formulations.
• Competitive Advantage: Epclusa’s ease of use and lack of drug interactions make it a preferred option for many patients.

FAQs

1. What is Epclusa, and how does it work? Epclusa is a fixed-dose combination of sofosbuvir and velpatasvir, targeting the HCV non-structural proteins NS5B and NS5A, respectively. It is used to treat chronic HCV infection across all genotypes.

2. What are the common adverse reactions associated with Epclusa? The most common adverse reactions are headache and fatigue, with a safety profile similar to placebo treatment.

3. Is Epclusa approved for pediatric use? Yes, Epclusa is approved for children as young as 3 years old, with different formulations available for younger children who cannot swallow tablets.

4. How effective is Epclusa in treating HCV infection? Epclusa has demonstrated high SVR12 rates across all HCV genotypes, with overall rates of up to 98% in adult populations and significant cure rates in pediatric populations.

5. What is the market share of Epclusa in the US HCV treatment market? As of the first half of 2024, Epclusa held approximately 56% of the new prescription market share in the US.

Sources

1. US Food And Drug Administration Approves Epclusa Sofosbuvir ... - Gilead.
2. Third Quarter Financial and Business Update - Atea Pharma.
3. Summary Basis of Decision for Epclusa - Health Canada.
4. U.S. Food and Drug Administration Approves New Formulation of Epclusa - Gilead.
5. Gilead Sciences Announces Second Quarter 2024 Financial Results - Gilead.