Protease inhibitors |
Telaprevir |
II |
(dose-750 mg q8h; genotype-1) |
Low level: V36A/M, T54A, R155K/T, A156S |
Rash, GI and hematological adverse events (AE) |
|
(VX-950) |
PROVE- 1, 2, 3 |
VLR = 3 log d 3 |
High level: A156V/T, V36A/M-R155K/T, V36A/M-A156V/T; |
|
|
|
VLR = 4.4 log: d 14 |
After 14 d of treatment |
|
|
|
VLR = 5.5 log: d 14 when combined with PEG-IFNa2a |
|
SCH 503034 |
II |
(dose 400 mg q8h; genotype-1) |
Low to moderate levels: |
Frequency of AE comparable to control group receiving placebo |
|
|
|
VLR = 2.06 log d 14 |
V170A |
|
|
|
VLR = 2.9 log: when combined with PEG-IFN |
T54A |
|
|
|
|
A156S |
|
|
|
|
High level: A156T |
Inhibitor of protease cofactor NS4A |
ACH-806 |
I/II |
VLR = 1 log: d 5 |
Single mutation at N-terminus of NS3; lack of cross resistance to any of the polymerase inhibitors or protease inhibitors now under development |
Reversible nephrotoxicity |
Polymerase inhibitors |
Valopicitabine (NM283) |
II |
VLR = 0.8 log: d 28 |
S282T |
GI and hematological AE |
|
|
|
VLR = 2.7 log: d 28, when combined with PEG-IFN |
|
|
|
VLR = 4.24 log: wk 24, when combined with PEG-IFN |
|
R1479 (R1626) |
II |
VLR = 3.7 log for 4500 mg q12h at d 14, VLR = 2.6 log for 3000 mg q12h |
no data |
Mild to moderate hematological AE with increasing doses |
|
HCV-796 |
II |
VLR = 1.4-1.5 log: d 4 |
C316Y |
Mild to moderate headache-the most frequent AE; no treatment-emergent serious AE |
|
|
|
VLR = 3.3-3.5 log: d 14, when combined with PEG-IFN |
|
BILB 1941 |
I |
Data incomplete due to high discontinuation rate |
No data |
GI AE |
Cyclophilin inhibitors |
DEBIO 025 |
I |
VLR = 3.6 log: d 14 of monotherapy |
No breakthrough during the treatment |
Transitional hyperbilirubinemia |