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 with EPCLUSA:
a protease inhibitor–free regimen

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.1 Achieving SVR12 is considered a virologic cure.2

Real-world integrated analysis

99%

OVERALL CURE RATE3

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)

Largest real-world analysis of DAA HCV regimens3

Largest real-world analysis of DAA HCV regimens3

  • Patients who did not achieve SVR12/24 due to non-virological (n=332) or unknown (n=24) reasons were excluded from the effectiveness population3
  • Patients achieved high cure rates across diverse subgroups, including those with GT 3 (n=1649/1677) and CCa (n=1055/1078)3
  • 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 history3

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.

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

Trial Safety Data

  • Adverse reactions reported in ≥5% of patients in ASTRAL-1 study: headache (22%), fatigue (15%), nausea (9%), asthenia (5%), and insomnia (5%)1
  • The adverse reactions observed in patients 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-31
  • Influenza-like illness was also observed in ≥5% of subjects treated with EPCLUSA in the Real-World Integrated Analysis4,a

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

A pangenotypic and panfibrotic treatment with consistent outcomes1,5

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.

EPCLUSA DEMONSTRATED CURE IN PEOPLE WHO INJECT DRUGS, INCLUDING THOSE RECEIVING MEDICATION-ASSISTED TREATMENT (MAT)1


94%

OVERALL CURE RATE1

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


100%

OVERALL CURE RATE in mITT6,7

in GT 1-4 NC/CC adult patients
(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%].6,7

SVR12 was the primary endpoint (HCV RNA <LLOQ 12 weeks after treatment completion). Achieving SVR12 is considered a virologic cure.1,2

The mITT analysis is not presented in the EPCLUSA full Prescribing Information and the SIMPLIFY publication.

This mITT analysis was not in the original statistical plan and should be considered descriptive only.
Therefore, the results require cautious interpretation and could represent chance findings.

Trial 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

EPCLUSA provided a consistent cure in people who inject drugs with varied adherence6

Important attributes to address the challenges of injection drug use

Protease inhibitor-free medication icon
Protease inhibitor–free1
Knife and fork icon
No food requirement in NC/CC patients, so patients can take with or without food1
Puzzle pieces icon
Effective with concurrent
medication-assisted treatment1
Pill bottle icon
Available in monthly bottles, which may enable patients with unstable housing to be discreet1
Pill icon
Minimal pill burden1
One pill, once a day for 12 weeks in NC/CC patients

A protease inhibitor–free regimen for your hepatitis C patients who inject drugs1,6

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

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 patients 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 patients with HCV and ESRD requiring dialysis (Trial 4062) was nausea (7%)

ALTHOUGH USE WITH PPIs IS NOT RECOMMENDED, EPCLUSA CAN BE USED WITH OMEPRAZOLE WHEN MEDICALLY NECESSARY 1

Consistent outcomes with or without PPIs1,9

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

97%

CURE RATE9

with a PPI
(n=84/87)

97%

CURE RATE9

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 Data9

  • 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% (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 AE9

Cure = sustained virologic response (SVR12; HCV RNA <LLOQ 12 weeks after treatment completion).2

See Safety Profile
See Access and Support

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 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 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; DAA = direct-acting antiviral; DDI = drug-drug interaction; ESRD = end-stage renal disease; F0-F2 = stages 0-2 fibrosis; F3 = stage 3 fibrosis; F4 = stage 4 fibrosis; GT = genotype; ITT = intent to treat; LLOQ = lower limit of quantification; NC = non-cirrhotic; PI = protease inhibitor; PP = per protocol; PPI = proton-pump inhibitor; SAE = serious adverse event; 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. 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
  3. 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.
  4. Data on file. Data for Real-World Integrated Analysis.
  5. Lawitz E, Bourlière; M, Han L, et al. Poster presented at: International Liver Congress; April 19-23, 2017; Amsterdam, Netherlands.
  6. 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.
  7. Data on file. Gilead Sciences. April 2022.
  8. Liverpool Drug Interactions Group, University of Liverpool. Interactions charts for HCV DAAs and ribavirin. HEP Drug Interactions. Updated March 14, 2022. Accessed March 14, 2022. https://www.hep-druginteractions.org/prescribing-resources.
  9. 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.