Download sofosbuvir/velpatasvir

®
Epclusa
sofosbuvir/velpatasvir
Manufacturer: Gilead Sciences, Inc
FDA Approval Date: June 28, 2016
Kelsy Combs, PharmD
Epclusa® - sofosbuvir/velpatasvir
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Epclusa® -
(sofosbuvir/velpatasvir)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Epclusa® (sofosbuvir/velpatasvir)
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 (ChildPugh B or C) in combination with
ribavirin (RBV)
Epclusa [package insert].
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].
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].
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].
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].
Epclusa® - sofosbuvir/velpatasvir
Drug Facts
• Pharmacokinetics:
Sofosbuvir
0.5-1h
Velpatasvir
3h
Effect of high fat meal
(relative to fasting)
78%
21%
% Bound
Blood to plasma ratio
61-65
0.7
>99.5
0.52-0.67
M
Metabolism
Active Metabolite GS461203; Inactive Metabolite
GS-331007
CYP2B6
CYP2C8
CYP3A4
E
% Urine
% Fecal
T1/2 (h)
A
D
Tmax
SOF: 0.5;
80
14
GS-331007: 25
0.4
94
15
Epclusa [package insert].
Epclusa® - sofosbuvir/velpatasvir
Drug Interactions
• Drug Interactions – Object Drugs:
• May increase the concentration of:
• Topotecan
• Digoxin
• Tenofovir
• Rosuvastatin
• Atorvastatin
Epclusa [package insert].
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].
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; 373:2599-607.
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].
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].
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
• sofosbuvir 400 mg/velpatasvir 100 mg PO
once daily for 12 weeks
• Cost: – $29904 / 28 tablets
• Source – UpToDate 9/26/16
Epclusa [package insert].
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; 373:2608-17.
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; 373:2608-17.
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; 373:2608-17.
Epclusa® - sofosbuvir/velpatasvir
Literature Review
• Patient Characteristics
HCV Genotype 2
57
60
HCV Genotype 3
50
62
White (%)
HCV RNA Mean
(log10 IU/mL)
87
6.5
88
6.2
Compensated
Cirrhosis (%)
Previous HCV Tx
14
29
14
26
Mean age (yr)
Male sex (%)
Foster, G.R., et al. N Engl J Med 2015; 373:2608-17.
Epclusa® - sofosbuvir/velpatasvir
Literature Review
• Efficacy
HCV RNA
<15 IU/mL
(End of Tx)
At 4 wk
At 12 wk
Absolute
Difference
HCV Genotype 2
Sofosbuvir/ Sofosbuvir/
Velpatasvir Ribavirin x
x 12 wks
12 wks
HCV Genotype 3
Sofosbuvir/ Sofosbuvir/
Velpatasvir Ribavirin x
x 12 wks
24 wks
(N=134)
(N=132)
(N=277)
(N=275)
133 (99)
133 (99)
127 (96)
124 (94)
268 (97)
264 (95)
225 (82)
221 (80)
5.2% (95% CI 0.2-10.3)
p=0.02
14.8% (95% CI 9.6-20.0)
p<0.001
Foster, G.R., et al. N Engl J Med 2015; 373:2608-17.
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; 373:2608-17.
Epclusa® - sofosbuvir/velpatasvir
Literature Review
• Adverse Effects
Any ADE N (%)
Fatigue N (%)
Headache
N (%)
Hgb < 10 g/dL
N (%)
HCV Genotype 2
Sofosbuvir/ Sofosbuvir/
Velpatasvir Ribavirin x
x 12 wks
12 wks
92 (69)
101 (77)
20 (15)
47 (36)
HCV Genotype 3
Sofosbuvir/ Sofosbuvir/
Velpatasvir Ribavirin x
x 12 wks
24 wks
245 (88)
260 (95)
71 (26)
105 (38)
24 (18)
29 (22)
90 (32)
89 (32)
0 (0)
6 (5)
0 (0)
10 (4)
Foster, G.R., et al. N Engl J Med 2015; 373:2608-17.
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; 373:2608-17.
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.
Epclusa® - sofosbuvir/velpatasvir
References
1.
https://www.epclusainfo.com/
2.
Epclusa (sofosbuvir and velpatasvir) [prescribing
information]. Foster City, CA: Gilead Sciences Inc; June
2016.
3.
Feld, J.J, et al. Sofosbuvir and velpatasvir for hcv genotype
1, 2, 3, 4, 5, and 6 infection. N Engl J Med 2015; 373:2599607.
4.
Foster, G.R., et al. Sofosbuvir and velpatasvir for hcv
genotype 2 and 3 infection. N Engl J Med 2015; 373:2608-17.
5.
Curry, M.P., et al. Sofosbuvir and velpatasvir for hcv in
patients with decompensated cirrhosis. N Engl J Med 2015;
373:2618-28.