1. Epclusa® sofosbuvir/velpatasvir
Manufacturer: Gilead Sciences, Inc
FDA Approval Date: June 28, 2016
Kelsy Combs, PharmD

2. Epclusa® - sofosbuvir/velpatasvir Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Epclusa® - (sofosbuvir/velpatasvir)
Effectively educate patients on the purpose, proper use and potential adverse effects of Epclusa® - (sofosbuvir/velpatasvir)

3. Epclusa® - sofosbuvir/velpatasvir Clinical Application
Indications:
Treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6
Without cirrhosis or with compensated cirrhosis (Child-Pugh A)
With decompensated cirrhosis (Child-Pugh B or C) in combination with ribavirin (RBV)
Epclusa [package insert].

4. Epclusa® - sofosbuvir/velpatasvir Clinical Application
Place in therapy:
An option for 1st line treatment of any genotype HCV infection without cirrhosis, with compensated cirrhosis, or decompensated cirrhosis
Epclusa [package insert].

5. Epclusa® - sofosbuvir/velpatasvir Clinical Application
Contraindications (Ribavirin):
Hemoglobinapathy
Pregnancy
Warnings: (and Black Box warnings)
Ribavirin may cause hemolytic anemia which can worsen cardiac disease
Precautions:
Bradycardia in patients taking amiodarone
Epclusa [package insert].

6. Epclusa® - sofosbuvir/velpatasvir Clinical Application
Pregnancy:
RBV - Contraindicated in pregnant women and men whose female partners are pregnant
Sofosbuvir/velpatasvir – No human data
Lactation:
Unknown if excreted in human breast milk
Excreted in milk of treated rats
Epclusa [package insert].

7. Epclusa® - sofosbuvir/velpatasvir Drug Facts
Pharmacology:
Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor
RNA chain terminator
Velpatasvir prevents viral replication via inhibition of NS5A protein
Epclusa [package insert].

8. Epclusa® - sofosbuvir/velpatasvir Drug Facts
Pharmacokinetics:
Sofosbuvir
Velpatasvir A
Tmax
0.5-1h
3 h
Effect of high fat meal (relative to fasting)
78%
21% D
% Bound
61-65
>99.5
Blood to plasma ratio
0.7 M
Metabolism
Active Metabolite GS ; Inactive Metabolite GS
CYP2B6
CYP2C8
CYP3A4 E
% Urine 80
0.4
% Fecal 14 94
T1/2 (h)
SOF: 0.5; GS : 25 15
Epclusa [package insert].

9. Epclusa® - sofosbuvir/velpatasvir Drug Interactions
Drug Interactions – Object Drugs:
May increase the concentration of:
Topotecan
Digoxin
Tenofovir
Rosuvastatin
Atorvastatin
Epclusa [package insert].

10. Epclusa® - sofosbuvir/velpatasvir Drug Interactions
Drug Interactions – Precipitant Drugs:
Antacids, H2RA, PPI and efavirenz may decrease the concentration of velpatasvir
Carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifampin, tipranavir/ritonavir and St. Johns wort may decrease sofosbuvir/velpatasvir
Epclusa [package insert].

11. Epclusa® - sofosbuvir/velpatasvir Adverse Effects
Common Adverse Effects: (sofosbuvir/velpatasvir%) [placebo%]
Headache (29) [28]
Fatigue (20) [20]
Nasopharyngitis (13) [10]
Nausea (12) [11]
Diarrhea (8) [7]
Asthenia (7) [8]
Feld, J.J, et al. N Engl J Med 2015; 373:

12. Epclusa® - sofosbuvir/velpatasvir Monitoring Parameters
Efficacy Monitoring:
Reduction in HCV RNA viral load
Toxicity Monitoring:
RBV – Hemoglobin
At baseline, weeks 2 and 4
Epclusa [package insert].

13. Epclusa® - sofosbuvir/velpatasvir Prescription Information
Dosing:
Patients w/o cirrhosis and with compensated cirrhosis (Child-Pugh A)
sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks
Patients with decompensated cirrhosis
sofosbuvir 400 mg/velpatasvir 100 mg once daily + Ribavirin for 12 weeks
Epclusa [package insert].

14. Epclusa® - sofosbuvir/velpatasvir Prescription Information
Dosing:
Patients w/o cirrhosis and with compensated cirrhosis (Child-Pugh A)
sofosbuvir 400 mg/velpatasvir 100 mg PO once daily for 12 weeks
Patients with decompensated cirrhosis
Cost: – $29904 / 28 tablets
Source – UpToDate 9/26/16
Epclusa [package insert].

15. Epclusa® - sofosbuvir/velpatasvir Literature Review
Sofosbuvir and Velpatasvir for HCV genotype 2 and 3 Infection (ASTRAL-2 and ASTRAL-3)
Design
Randomized, open-label, phase 3 trial
Assigned 1:1 ratio to:
Sofosbuvir 400 mg/velpatasvir 100 mg once daily x 12 weeks OR
Sofosbuvir 400 mg + Ribavirin for 12 weeks (genotype 2) or 24 weeks (genotype 3)
Foster, G.R., et al. N Engl J Med 2015; 373:

16. Epclusa® - sofosbuvir/velpatasvir Literature Review
Inclusion Criteria
ASTRAL 2 – HCV genotype 2
ASTRAL 3 – HCV genotype 3
≥ 18 YO
6 month history of HCV
Treatment naive or previous treatment with interferon based regimen
With or without compensated cirrhosis
Foster, G.R., et al. N Engl J Med 2015; 373:

17. Epclusa® - sofosbuvir/velpatasvir Literature Review
Primary Endpoint
Sustained virologic response at 12 weeks
HCV RNA level <15 IU/mL
After the end of treatment
Foster, G.R., et al. N Engl J Med 2015; 373:

18. Epclusa® - sofosbuvir/velpatasvir Literature Review
Patient Characteristics
HCV Genotype 2
HCV Genotype 3
Mean age (yr) 57 50
Male sex (%) 60 62
White (%) 87 88
HCV RNA Mean (log10 IU/mL)
6.5
6.2
Compensated Cirrhosis (%) 14 29
Previous HCV Tx 26
Foster, G.R., et al. N Engl J Med 2015; 373:

19. Epclusa® - sofosbuvir/velpatasvir Literature Review
Efficacy
HCV Genotype 2
HCV Genotype 3
HCV RNA <15 IU/mL
(End of Tx)
Sofosbuvir/Velpatasvir x 12 wks
(N=134)
Sofosbuvir/Ribavirin x 12 wks
(N=132)
(N=277)
Sofosbuvir/Ribavirin x 24 wks
(N=275)
At 4 wk
133 (99)
127 (96)
268 (97)
225 (82)
At 12 wk
124 (94)
264 (95)
221 (80)
Absolute
Difference
5.2% (95% CI ) p=0.02
14.8% (95% CI ) p<0.001
Foster, G.R., et al. N Engl J Med 2015; 373:

20. Epclusa® - sofosbuvir/velpatasvir Literature Review
SVR12 According to Cirrhosis Status and Previous Treatment in Genotype 3
Foster, G.R., et al. N Engl J Med 2015; 373:

21. Epclusa® - sofosbuvir/velpatasvir Literature Review
Adverse Effects
HCV Genotype 2
HCV Genotype 3
Sofosbuvir/Velpatasvir x 12 wks
Sofosbuvir/Ribavirin x 12 wks
Sofosbuvir/Ribavirin x 24 wks
Any ADE N (%)
92 (69)
101 (77)
245 (88)
260 (95)
Fatigue N (%)
20 (15)
47 (36)
71 (26)
105 (38)
Headache
N (%)
24 (18)
29 (22)
90 (32)
89 (32)
Hgb < 10 g/dL N (%)
0 (0)
6 (5)
10 (4)
Foster, G.R., et al. N Engl J Med 2015; 373:

22. Epclusa® - sofosbuvir/velpatasvir Literature Review
Conclusions
Sofosbuvir/velpatasvir has superior efficacy in rates of SVR12 in patients with HCV genotype 2 or 3 including those:
with or without previous treatment
with or without compensated cirrhosis
Sofosbuvir/velpatasvir has lower rates of adverse drug events than sofosbuvir/ribavirin
Foster, G.R., et al. N Engl J Med 2015; 373:

23. Epclusa® - sofosbuvir/velpatasvir Summary
Epclusa® is indicated for once daily treatment of chronic HCV genotype 1, 2, 3, 4, 5, or 6
Dosing is sofosbuvir 400 mg / velpatasvir 100 mg by mouth daily for 12 weeks for patients without cirrhosis and patients with compensated cirrhosis. Ribavirin is added for 12 weeks for patients with decompensated cirrhosis.
Ribavirin may cause hemolytic anemia. Monitor hemoglobin (at baseline, weeks 2 & 4, then periodically) in patients with decompensated cirrhosis coadministered ribavirin.

24. Epclusa® - sofosbuvir/velpatasvir References
Epclusa (sofosbuvir and velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; June
Feld, J.J, et al. Sofosbuvir and velpatasvir for hcv genotype 1, 2, 3, 4, 5, and 6 infection. N Engl J Med 2015; 373:
Foster, G.R., et al. Sofosbuvir and velpatasvir for hcv genotype 2 and 3 infection. N Engl J Med 2015; 373:
Curry, M.P., et al. Sofosbuvir and velpatasvir for hcv in patients with decompensated cirrhosis. N Engl J Med 2015; 373: