Robust Clinical Trials^1-3

Randomized trials in TN and TE adult chronic HCV patients without cirrhosis or with compensated cirrhosis

Patients who were active injection drug users (use within 12 months), or those with a positive urine drug test at screening, were excluded from the ASTRAL pivotal trials.

ASTRAL-1: Double-blind, placebo-controlled trial in GT 1, 2, 4, 5, or 6 patients (N=740). GT 1, 2, 4, or 6 patients were randomized 5:1 to receive EPCLUSA or placebo for 12 weeks; GT 5 patients received EPCLUSA for 12 weeks.

ASTRAL-2: Open-label trial in GT 2 patients (N=266). Patients received EPCLUSA or SOF + RBV for 12 weeks.

ASTRAL-3: Open-label trial in GT 3 patients (N=552). Patients received EPCLUSA for 12 weeks or SOF + RBV for 24 weeks.

TE patients had failed a Peg-IFN + RBV-based regimen with or without an HCV NS3/4A protease inhibitor (boceprevir, simeprevir, or telaprevir).

Sustained virologic response (SVR12) was the primary endpoint for all clinical trials and was defined as HCV RNA <15 IU/mL at 12 weeks after the end of treatment.

Real-World Study⁴

Real-World Integrated Analysis: A retrospective, pooled analysis of SVR12/24 in adult NC/CC chronic HCV patients treated for 12 weeks with EPCLUSA (400 mg/100 mg) once-daily without RBV in 12 real-world cohorts in Canada, Europe, and the US (N=5552) (ANRS-Hepather, Borgia, DHC-R, Greek Cohort, HCV-TARGET, HepaC, HELIOS, Mangia, NAVIGATORE-II, Ramji, Shafran, TRIO Health). TN patients and patients who had previously received IFN-based therapy (Peg-IFN + RBV with or without telaprevir, boceprevir or simeprevir) were included. DC patients and patients who had previously failed other DAA treatments were excluded. Patients were treated in different clinical settings, including university hospitals, academic centers, community centers, outpatient clinics and private practices. Treatment and patient monitoring were based on local clinical practice and standard of care, at the discretion of the treating physician.

The Real-World Integrated Analysis is not presented in the EPCLUSA full Prescribing Information.

Real-world data are observational in nature and are not based on controlled clinical studies. Results from the Real-World Integrated Analysis may differ from those observed in clinical practice.

The Real-World Integrated Analysis was supported by Gilead Sciences, Inc.

Robust Clinical Trials

Randomized trials in TN and TE adult chronic HCV patients without cirrhosis or with compensated cirrhosis

Patients who were active injection drug users (use within 12 months), or those with a positive urine drug test at screening, were excluded from the ASTRAL pivotal trials.

ASTRAL-1: Double-blind, placebo-controlled trial in GT 1, 2, 4, 5, or 6 patients (N=740). GT 1, 2, 4, or 6 patients were randomized 5:1 to receive EPCLUSA or placebo for 12 weeks; GT 5 patients received EPCLUSA for 12 weeks.

ASTRAL-2: Open-label trial in GT 2 patients (N=266). Patients received EPCLUSA or SOF + RBV for 12 weeks.

ASTRAL-3: Open-label trial in GT 3 patients (N=552). Patients received EPCLUSA for 12 weeks or SOF + RBV for 24 weeks.

POLARIS-2: Open-label comparator trial in GT 1-6 DAA-naïve patients (N=941) who were randomized to receive EPCLUSA for 12 weeks or sofosbuvir/velpatasvir/voxilaprevir for 8 weeks.

POLARIS-3: Open-label comparator trial in DAA-naïve GT 3 cirrhosis patients (N=219) who were randomized to receive EPCLUSA for 12 weeks or sofosbuvir/velpatasvir/voxilaprevir for 8 weeks.

TE patients had failed a Peg-IFN + RBV-based regimen with or without an HCV NS3/4A protease inhibitor (boceprevir, simeprevir, or telaprevir).

Sustained virologic response (SVR12) was the primary endpoint for all clinical trials and was defined as HCV RNA <15 IU/mL at 12 weeks after the end of treatment.

ROBUST CLINICAL AND REAL-WORLD STUDIES SPECIFIC TO PEOPLE WHO INJECT DRUGS

SIMPLIFY¹

Simplify was an open-label, single-arm, international Phase 4 trial aimed at evaluating the efficacy, safety, and adherence of EPCLUSA for 12 weeks in GT 1-6 adults with recent injection drug use (within 6 months) and naïve to NS5A-based HCV therapy (N=103). Patients with HIV and/or decompensated liver disease were excluded. The primary endpoint was the proportion of participants with SVR12. Adherence (≥90%) was a secondary endpoint and was assessed by dividing the number of total doses received by total expected number of doses.

Study Limitations: Weekly clinic visits and weekly electronic blister packs, which patients were incentivized to return, may have led to improved adherence, which may not be generalizable to the larger HCV population. The study population in SIMPLIFY was recruited from hospital-based and community-based clinics/centers; it may not be generalizable to all populations of people with injection drug use.

Anchor²

Anchor was a prospective, open-label, observational, single-site trial evaluating the efficacy and adherence of EPCLUSA for 12 weeks in adults with opioid use disorder who reported ongoing injection drug use (within 3 months of screening visit) treated at a harm-reduction center in Washington, DC (N=100). Participants were offered optional buprenorphine initiation. Patients with decompensated liver disease and those who were pregnant or breastfeeding were excluded. The primary endpoint was the proportion of participants with SVR12. Adherence was assessed by monthly pill count, HCV VL, number of bottles completed, interruptions on treatment (≥3 days with resumption), and date of last pill taken relative to planned end-of-treatment date. Imperfect daily adherence was defined as finishing treatment >7 days after the anticipated treatment end date.

Study Limitations: OAT status groups were non-randomized and self-selected. Factors associated with non-uptake or discontinuation of OAT may have been the same factors that led to HCV treatment failure or loss to follow-up. Results may not be generalizable to the larger HCV population.

The SIMPLIFY and ANCHOR studies are not presented in the EPCLUSA full Prescribing Information.

ESRD Clinical Trial¹

Single-arm trial of TN and TE adults with ESRD without cirrhosis or with compensated cirrhosis

Trial 4062: Open-label clinical trial in NC/CC patients with GT 1, 2, 3, 4, 6 or indeterminate HCV infection with ESRD requiring dialysis (N=59). Subjects received EPCLUSA for 12 weeks.

TE patients had failed a Peg-IFN + RBV or IFN + RBV-based regimen.

Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA <LLOQ at 12 weeks after the end of treatment.

The PPI analysis was a retrospective evaluation of the safety and efficacy of EPCLUSA with or without concomitant PPI use in GT 1-6 adults treated for 12 weeks in 12 previously completed Phase 2 or 3 clinical trials. This integrated analysis included TN and TE patients with or without cirrhosis (N=2604). PPI use was captured as part of the standard concomitant medication reporting, and specific details regarding PPI dosing were not collected. 87 patients (3.3%) were treated with PPIs. Of the patients taking PPIs, 60 were subjects in Phase 2 studies, including 20 GT 3 cirrhotic patients in Spain and 40 post-liver-transplant adult patients. PPIs included in the analysis were: omeprazole (68%), pantoprazole (13%), esomeprazole (13%), lansoprazole (5%), dexlansoprazole (2%), and rabeprazole (1%).

Results from the PPI analysis are not presented in the EPCLUSA full Prescribing Information.