EPCLUSA (sofosbuvir 400 mg/velpatasvir 100 mg, sofosbuvir 200 mg/velpatasvir 50 mg tablets) is indicated for the treatment of patients 6 years of age and older or weighing at least 17 kg with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 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

A real cure for the broad range of CHRONIC HCV patients you see1,2

A protease inhibitor–free regimen with consistent outcomes
in clinical trials and real-world studies1,3

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.4

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 and effectiveness populations and stratified by fibrosis stage, previous or current intravenous drug use, and treatment history3

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.

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

Trial Safety Data

  • Adverse reactions reported in ≥5% of patients in ASTRAL-1: 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 patients treated with EPCLUSA in ASTRAL-31
  • Influenza-like illness was also observed in ≥5% of patients treated with EPCLUSA in the Real-World Integrated Analysis5,b

bDerived 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 outcomes1-3

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.

EPCLUSA DEMONSTRATED HIGH CURE RATES IN PEOPLE WHO INJECT DRUGS IN SIMPLIFY AND ANCHOR6,7

Simplify Clinical Study

94%

cure rate6

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

ANCHOR real-world study

88%

cure rate7

in GT 1-4 NC/CC adult patients
(n=82/93; PP)

For the total patient population, the cure rate was 82% (n=82/100).

Both studies had a primary endpoint of SVR12 (HCV RNA <LLOQ 12 weeks after treatment completion). Achieving SVR12 is considered a virologic cure.4,6,7

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

Trial Safety Data6,8

  • Adverse reactions in SIMPLIFY reported in ≥5% of patients were: fatigue (22%), headache (18%), nausea (14%), insomnia (9%), arthralgia (6%), dizziness (5%), and nasopharyngitis (5%)
  • Seven (7%) patients in SIMPLIFY had at least one SAE, and 1 (1%) SAE was considered treatment-related
  • Per study protocol, adverse reaction data in ANCHOR were not collected

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

  • 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 trials9,10
  • Patients in SIMPLIFY and ANCHOR were instructed to use EPCLUSA once daily for 12 weeks as recommended in the EPCLUSA full Prescribing Information. In SIMPLIFY, patients received EPCLUSA in weekly blister packs1,6,7
  • Real-world data are observational in nature and are not based on controlled clinical studies. Results from these studies may differ from those observed in clinical practice. The SIMPLIFY and ANCHOR studies were supported by Gilead Sciences, Inc.

Main Takeaways7

  • All participants self-reported injection drug use within 3-6 months of enrollment
  • Many participants were concurrently on medication-assisted treatment
  • Impact of adherence on efficacy with EPCLUSA was assessed

Real attributes for the real challenges associated with injection drug use

Needle icon
No known interactions with: Opioids oxycodone and fentanyl; Antipsychotics aripiprazole (ABILIFY), clozapine (CLOZARIL), and quetiapine (SEROQUEL)11
See Safety Profile for DDIs
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 treatment6
Protease inhibitor-free medication icon
Protease inhibitor–free1
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 HCV patients who inject drugs1,6,7

Real proof in 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 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 necessary1

Consistent outcomes with or without PPIs12

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

97%

cure rate12

with a PPI
(n=84/87)

97%

cure rate12

without a PPI
(n=2445/2517)

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

Trial Safety Data12

  • 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 AE12

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

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, sofosbuvir 200 mg/velpatasvir 50 mg tablets) is indicated for the treatment of patients 6 years of age and older or weighing at least 17 kg with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 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 were headache and fatigue; and when used with RBV in decompensated cirrhotics were fatigue, anemia, nausea, headache, insomnia, and diarrhea.

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, sofosbuvir 200 mg/velpatasvir 50 mg tablets) is indicated for the treatment of patients 6 years of age and older or weighing at least 17 kg with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 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; July 2020.
  2. Lawitz E, Bourlière M, Han L, et al. Poster presented at: International Liver Congress; April 19-23, 2017; Amsterdam, Netherlands.
  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. Published online May 25, 2020. doi:10.1111 liv.14537.
  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. Data for Real-World Integrated Analysis. Accessed August 2020.
  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. Rosenthal E, Silk R, Mathur P, et al. Concurrent initiation of hepatitis C and opioid use disorder treatment in people who inject drugs. Clin Infect Dis. Published online February 3, 2020. doi:10.1093/cid/ciaa105. Accessed June 5, 2020.
  8. Data on file. Data for ANCHOR. Accessed October 8, 2020.
  9. Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infections. N Eng J Med. 2015;373:2599‐2607.
  10. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Eng J Med. 2015;373:2608‐2617.
  11. Liverpool Drug Interactions Group, University of Liverpool. Interactions charts for HCV DAAs and ribavirin. HEP Drug Interactions. Updated March 2020. Accessed May 4, 2020. https://www.hep-druginteractions.org/prescribing-resources.
  12. 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.