INDICATION

EPCLUSA (sofosbuvir 400 mg/velpatasvir 100 mg, 200 mg/50 mg tablets; 200 mg/50 mg, 150 mg/37.5 mg oral pellets) is indicated for the treatment of patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1-6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis.

Please see below for Important Safety Information for EPCLUSA.

Efficacy

CONFIDENTLY CURE YOUR CHRONIC HCV PATIENTS WITH EPCLUSA OR ITS AUTHORIZED GENERIC1

(sofosbuvir/velpatasvir)

Featured patients compensated by Gilead.

SIMPLIFY CURE RATES

ONLY EPCLUSA HAS

100%

OVERALL CURE RATE (mITT) IN PEOPLE WHO INJECT DRUGS AMONG PANGENOTYPIC REGIMENS2,3

GT 1-4 NC/CC (n=97/97;
SIMPLIFY study)

mITT = modified intent-to-treat excludes 1 reinfection and 5 patients who did not meet virologic failure criteria [SVR rate 95% CI: 96%-100%].1,3

This post-hoc mITT analysis of patients from the SIMPLIFY trial was not in the original statistical plan and should be considered descriptive only. The mITT analysis is not presented in the EPCLUSA full Prescribing Information or the SIMPLIFY publication.

94%

OVERALL CURE RATE (ITT) IN PEOPLE WHO INJECT DRUGS WITH CHRONIC HCV1

GT 1-4 NC/CC (n=97/103;
SIMPLIFY study)

SVR12 was the primary endpoint in the SIMPLIFY study (HCV RNA <LLOQ 12 weeks after treatment completion). Achieving SVR12 is considered a virologic cure.1,4

SIMPLIFY STUDY SAFETY DATA1

  • The most common adverse reactions in SIMPLIFY were fatigue (18%), nausea (13%), and headache (11%)
  • Adverse reactions leading to permanent discontinuation of treatment were not observed in any subjects

ONLY EPCLUSA HAS

A 100% CURE RATE (mITT) IN ALL THESE SUB-POPULATIONS (AMONG PANGENOTYPIC REGIMENS)5 :

100% CURE RATE

Syringe in circle
ANY INJECTION DRUG USE IN THE PAST 30 DAYS

(n=72/72; 95%
CI: 95%-100%)

100% CURE RATE

3 syringes in circle
At least daily injection drug use in the past 30 days

(n=26/26; 95%
CI: 87%-100%)

100% CURE RATE

Pill bottle in circle
Current mat

(n=54/54; 95%
CI: 93%-100%)

100% CURE RATE

Bottle and glass in circle
Alcohol use in the past 30 days

(n=60/60; 95%
CI: 94%-100%)

100% CURE RATE

Broken house in circle
Unstably housed

(n=22/22; 95%
CI: 85%-100%)

100% CURE RATEa

Virus icon in circle
GENOTYPE 3

(n=57/57; 95%
CI: 94%-100%)

(n=97; SIMPLIFY study)3

a 95-97% cure rate in GT 3 patients receiving EPCLUSA (n=455/475) in the ASTRAL‑3 and POLARIS‑2 and -3 studies.1,6

SIMPLIFY STUDY INFORMATION AND LIMITATIONS1,3

  • mITT = modified intent-to-treat excludes 1 reinfection and 5 patients who did not meet virologic failure criteria [SVR rate 95% CI: 96%-100%]
  • Among the 6 excluded patients, 4 were on current MAT, 4 had IDU in the last 30 days, 3 had <90% adherence, 3 were GT 3, 3 were unstably housed, 2 had alcohol in the past 30 days, and 1 had daily IDU in the past 30 days
  • The post-hoc mITT analysis of patients from the SIMPLIFY trial was not in the original statistical plan and should be considered descriptive only
  • The mITT analysis is not presented in the EPCLUSA full Prescribing Information and the SIMPLIFY publication

SIMPLIFY ADHERENCE

In a study focused on people who injected drugs,a
CONSISTENT CURE FOR PEOPLE WITH IMPERFECT ADHERENCE2,5

ONLY EPCLUSA HAS

100%

CURE RATE (mITT) IN PEOPLE WITH IMPERFECT ADHERENCE IN A PWID-SPECIFIC STUDY2,3,5

(n=31/31; 95% CI: 89%-100%;
SIMPLIFY study)

Imperfect adherence = <90% adherence or >8 doses missed.2,7

mITT = modified intent-to-treat excludes 1 reinfection and 5 patients who did not meet virologic failure criteria [SVR rate 95% CI: 96%-100%]. Among the 6 excluded patients, 3 had <90% adherence.1,3

91%

CURE RATE (ITT) IN PEOPLE WITH IMPERFECT ADHERENCE IN A PWID-SPECIFIC STUDY1,2

(n=31/34; SIMPLIFY study)

Imperfect adherence = <90% adherence or >8 doses missed.2,7

SVR12 (cure) = HCV RNA <LLOQ 12 weeks after treatment completion.4

Overall median adherence: 94% (IQR 88-98).2

a In SIMPLIFY, “people who inject drugs” was defined as those who had injected drugs within the 6 months prior to study initiation.1

SIMPLIFY STUDY INFORMATION AND LIMITATIONS2

  • Patients in SIMPLIFY were instructed to use EPCLUSA once daily for 12 weeks as recommended in the EPCLUSA full Prescribing Information
  • Adherence was assessed by dividing the number of total doses received during therapy by the total expected number (84) of doses
  • Adherence may have been improved by weekly clinic visits and electronic blister packs, which patients were incentivized to return. Adherence was assumed when a blister pack was damaged in a way that prevented scanning, but no pills were returned
  • The post-hoc mITT analysis of patients from the SIMPLIFY trial was not in the original statistical plan and should be considered descriptive only
  • The mITT analysis and SIMPLIFY adherence data are not presented in the EPCLUSA full Prescribing Information. The mITT analysis is not presented in the SIMPLIFY publication

ASTRAL PIVOTAL STUDIES

HIGH CURE RATES ACROSS PIVOTAL AND REAL-WORLD STUDIES

IN PIVOTAL CLINICAL TRIALS

98%

OVERALL CURE RATE1 IN GT 1-6 TN/TE NC/CC ADULT PATIENTS

(n=1015/1035;
ASTRAL-1, -2, -3 studies)

SVR12 was the primary endpoint in EPCLUSA clinical trials and was defined as HCV RNA <15 IU/mL at 12 weeks after the end of treatment. Achieving SVR12 is considered a virologic cure.1,4

REAL-WORLD INTEGRATED ANALYSIS

99%

OVERALL CURE RATE8 IN EFFECTIVENESS POPULATION IN GT 1-6 TN/TE NC/CC PATIENTS

(n=5141/5196; pooled analysis of 12 clinical cohorts and studies in Canada, Europe, and the USA, PP)

Cure rate for the whole population was 93% (n=5141/5552, ITT).8

Largest real-world analysis of DAA HCV regimens8

  • Patients who did not achieve SVR12/24 due to non-virological (n=332) or unknown (n=24) reasons were excluded from the effectiveness population8
  • Patients achieved high cure rates across diverse subgroups, including those with GT 3 (n=1649/1677) and CCa (n=1055/1078)8
  • The primary outcome was SVR12/24 (HCV RNA <LLOQ 12 or 24 weeks after treatment completion), which was calculated in the overall effectiveness populations and stratified by fibrosis stage, previous or current intravenous drug use, PPI use at baseline, and treatment history8

The Real-World Integrated Analysis is not presented in the EPCLUSA (sofosbuvir/velpatasvir) 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.

a CC patients had a higher risk of not achieving a cure.

TRIAL SAFETY DATA

  • Adverse reactions reported in ≥5% of subjects in ASTRAL-1 study: headache (22%), fatigue (15%), nausea (9%), asthenia (5%), and insomnia (5%)1
  • The adverse reactions observed in subjects treated with EPCLUSA in ASTRAL-2 and ASTRAL-3 were consistent with those observed in ASTRAL-11
  • Irritability was also observed in ≥5% of subjects treated with EPCLUSA in ASTRAL-39
  • Influenza-like illness was also observed in ≥5% of subjects treated with EPCLUSA in the Real-World Integrated Analysis9,b

b Derived from the HCV-TARGET, HepaC, HELIOS, and Mangia cohorts. Adverse reaction data were not recorded in other cohorts.9

CURE RATES BY GENOTYPE AND FIBROSIS SCORE

A pangenotypic and panfibrotic treatment with consistent outcomes10

Cure rates from ASTRAL-1, -2, and -3 and POLARIS-2 and -3 studies

Genotype F0-F2 F3 F4 (CC)
GT 1-6 99%

(n=871/874)

 99%

(n=232/234)

 97%

(n=431/443)
GT 1 100%

(n=303/303)

 99%

(n=91/92)

 98%

(n=152/155)
GT 2 100%

(n=195/195)

 100%

(n=34/34)

 100%

(n=58/58)
GT 3 99%

(n=218/221)

 100%

(n=76/76)

 94%

(n=154/163)
GT 4-6 100%

(n=155/155)

 97%

(n=31/32)

 100%

(n=67/67)

Cure rates (SVR12) derived from a completer efficacy analysis of the ASTRAL-1, -2, and -3 and POLARIS-2 and -3 studies, which included all patients who were randomized, completed the assigned study treatment, and had HCV RNA data observed at post-treatment Week 12 or thereafter. Individual fibrosis stage efficacy is not presented in the EPCLUSA full Prescribing Information.

END-STAGE RENAL DISEASE

HIGH CURE RATES IN HCV PATIENTS WITH END-STAGE RENAL DISEASE (ESRD) REQUIRING DIALYSIS1

95%

CURE RATE1 IN GT 1, 2, 3, 4, AND 6 NC/CC ADULT PATIENTS WITH HCV AND ESRD REQUIRING DIALYSIS

(n=56/59; Trial 4062)

EPCLUSA (sofosbuvir/velpatasvir) can be used with no dosage adjustment in HCV patients with any stage of renal impairment, including those requiring dialysis.

No safety data are available in subjects with both decompensated cirrhosis and severe renal impairment, including ESRD requiring dialysis. Additionally, no safety data are available in pediatric patients with renal impairment.

TRIAL SAFETY DATA

  • The most common adverse reaction in adults with HCV and ESRD requiring dialysis (Trial 4062) was nausea (7%)

PROTON-PUMP INHIBITOR ANALYSIS

ALTHOUGH USE WITH PPIs IS NOT RECOMMENDED, EPCLUSA CAN BE USED WITH OMEPRAZOLE WHEN MEDICALLY NECESARY1

Consistent outcomes with or without PPIs1,11

In a retrospective analysis of 12 EPCLUSA Phase 2 and 3 trials in adults:

97%

CURE RATE11 WITH A PPI

(n=84/87)

97%

CURE RATE11 WITHOUT A PPI

(n=2445/2517)

  • Results from the PPI analysis are not presented in the EPCLUSA (sofosbuvir/velpatasvir) full Prescribing Information
  • If medically necessary, EPCLUSA should be administered with food and taken 4 hours before omeprazole 20 mg1

TRIAL SAFETY DATA11

  • Treatment-emergent AEs were reported in 78% (n=68/87) of patients with PPI use vs 66% (n=1662/2517) without PPI use; grade 3 or 4 treatment-emergent AEs were present in 8% (n=7/87) of patients with PPI use vs 2% (n=58/2517) without PPI use
  • SAEs were reported in 11% (n=10/87) of patients with PPI use vs 2% (n=45/2517) without PPI use; treatment-related SAEs were present in 0% of patients regardless of PPI use

1% of patients taking a PPI discontinued HCV treatment due to an AE11

Cure = sustained virologic response (SVR12; HCV RNA <LLOQ 12 weeks after treatment completion).4

Important Safety Information

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

INDICATION

EPCLUSA (sofosbuvir 400 mg/velpatasvir 100 mg, 200 mg/50 mg tablets; 200 mg/50 mg, 150 mg/37.5 mg oral pellets) is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1-6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis.

Contraindications

  • If EPCLUSA is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

  • Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir-containing regimen. In patients without alternative viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect Due to Concomitant Use of EPCLUSA with P-gp Inducers and/or Moderate to Strong Inducers of CYP2B6, CYP2C8 or CYP3A4: Rifampin, St. John’s wort, and carbamazepine are not recommended for use with EPCLUSA as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations.

Adverse Reactions

  • The most common adverse reactions (≥10%, all grades) with EPCLUSA in adults and pediatric patients 6 years of age and older were headache and fatigue; and when used with RBV in adults with decompensated cirrhosis were fatigue, anemia, nausea, headache, insomnia, and diarrhea. The most common adverse reactions (≥10%, grade 1 or 2) in pediatric patients less than 6 years of age were vomiting and spitting up the drug.

Drug Interactions

  • Coadministration of EPCLUSA is not recommended with topotecan due to increased concentrations of topotecan.
  • Coadministration of EPCLUSA is not recommended with proton-pump inhibitors, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir.

Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments.


Please see full Prescribing Information for EPCLUSA, including BOXED WARNING.

VIEW ALL

Important Safety Information

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

INDICATION

EPCLUSA (sofosbuvir 400 mg/velpatasvir 100 mg, 200 mg/50 mg tablets; 200 mg/50 mg, 150 mg/37.5 mg oral pellets) is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1-6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis.

AE = adverse event; CC = compensated cirrhosis; CI = confidence interval; DAA = direct-acting antiviral; ESRD = end-stage renal disease; F0-F2 = stages 0-2 fibrosis; F3 = stage 3 fibrosis; F4 = stage 4 fibrosis; GT = genotype; IQR = interquartile range; ITT = intent-to-treat; LLOQ = lower limit of quantification; mITT = modified intent-to-treat; NC = non-cirrhotic; PP = per protocol; PPI = proton-pump inhibitor; SAE = serious adverse event; SVR = sustained virologic response; SVR12 = sustained virologic response 12 weeks after treatment completion; SVR12/24 = sustained virologic response 12 or 24 weeks after treatment completion; TE = treatment-experienced; TN = treatment-naïve.

References:

  1. EPCLUSA [prescribing information]. Foster City, CA: Gilead Sciences, Inc; April 2022.
  2. Grebely J, Dalgard O, Conway B, et al. Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Lancet Gastroenterol Hepatol. 2018;3(3):153-161.
  3. Data on file. Gilead Sciences. April 2022.
  4. US Department of Health and Human Services, Center for Drug Evaluation and Research. Guidance for industry. Chronic hepatitis C virus infection: developing direct-acting antiviral drugs for treatment. November 2017.
  5. Data on file. Gilead Subgroup Statistical Analysis. December 2022.
  6. Jacobson IM, Lawitz E, Gane EJ, et al. Efficacy of 8 weeks of sofosbuvir, velpatasvir, and voxilaprevir in patients with chronic HCV infection: 2 phase 3 randomized trials. Gastroenterology. 2017;153(1):113-122.
  7. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. https://www.hcvguidelines.org. Updated October 24, 2022. Accessed September 15, 2023.
  8. Mangia A, Milligan S, Khalili M, et al. Global real-world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: analysis of 5552 patients from 12 cohorts. Liver Int. 2020;40(8):1841-1852.
  9. Data on file. Data for Real-World Integrated Analysis.
  10. Lawitz E, Bourlière M, Han L, et al. Poster presented at: International Liver Congress; April 19-23, 2017; Amsterdam, Netherlands.
  11. Esteban R, Agarwal K, Calleja J, et al. Sofosbuvir/velpatasvir is effective and safe in patients with concomitant proton pump inhibitor use in clinical studies. Poster presented at: AASLD The Liver Meeting®; November 9-13, 2018: San Francisco, CA.