Table 2.
Overview of clinical efficacy of NS5B NIs or NNIs polymerase inhibitors
| Polymerase inhibitors | Company | Current clinical phase | Number of patients | Dose per day | Duration of therapy | Viral response | Side effects | Active against HCV genotype |
|---|---|---|---|---|---|---|---|---|
| Nucleoside or nucleotide inhibitors | ||||||||
| RG-7128 Mericitabine32–34 | Roche | II | 408 | 1000 mg BID | NIs + PR 12 w + PR 12/36 w RGT |
Naïve: SVR24 G1/G4: 33%–51% | AE profile similar to PR | 1,4 |
| II | 166 | 1000 mg BID | NIs + PR 24 w ± PR 24 w RGT |
Naïve SVR 24: 57% | 1,4 | |||
| II | 25 | 1500 mg BID | NIs + PR 4 w + PR 20/40 w RGT |
Relapsers G2/3 SVR: 70% Null responders G2/3 SVR: 60% |
2,3 | |||
| GS-7977 Sofosbuvir35–39, 99–105 | Gilead | II | 25 | 400 mg QD | NIs + PR 12 w | Naïve SVR 12: 100% | AE profile similar to PR | 2,3 |
| II | 95 | ELECTRON 400 mg QD |
NIs + RBV 12 w + PR (4,8,12 w in total) INF-free: NIs + RBV 12 w |
Naïve GT2,3 SVR 12: 100% Naïve GT1: SVR: 84% Null-R GT1: SVR4: 11% |
2,3 1,2,3 |
|||
| 34 | INF-free : NI+NS5A.I (LDV)+RBV 12w | Naïve GT1: SVR12: 100% Null-R GT1: SVR12: 100% |
||||||
| 35 | INF-free : NI+NNI (GS 9669) +RBV 12w | Naïve GT1: SVR12: 92% Null-R GT1: SVR12: 100% |
||||||
| 71 | NIs + PR 12 w + PR (12/36 w) | Naïve GT1: SVR 12: 88%–91% | ||||||
| II | 332 | PROTON 200–400 mg QD |
NIs + PR 12 w ±NI 12 w or NI + RBV 12 w |
Naïve GT1: SVR24 : 87–89% | 1 | |||
| II | NI + PR 24 w | Naïve GT4,6 SVR24: 82%, 100% | ||||||
| 34 | ATOMIC | INF-free:NIs + LDV + RBV 12 w | Naïve GT1: SVR12: 100% | 1,4,6 | ||||
| II | 400mg QD | Naïve GT1: SVR12: 100% | ||||||
| III | 327 | NEUTRINO 400mg QD |
NI+PR 12w | Naïve GT1,4,5,6: SVR12: 90%; cirrhosis 80% |
||||
| Non nucleoside inhibitors | ||||||||
| NNI-Site 1 inhibitors BI 207 12740 | 400 mg TID 600 mg TID 800 mg TID |
NNIs + PR 28 days + PR 40 w | Naïve G1: RVR: 50% RVR: 57% RVR: 50% |
|||||
| II | 57 | Trt-experienced G1 | Nausea, vomiting, diarrhea, rash | 1 | ||||
| Bohringer Ingelheim | 400 mg TID 600 mg TID 800 mg TID |
RVR: 0% RVR: 22% RVR: 18% |
||||||
| NNI-Site 2 inhibitors Filibuvir41 | Pfizer | II | 35 | 200 mg BID300 mg BID 500 mg BID |
NNIs + PR 28 day + PR 44 w | Naïve G1 RVR: 60% SVR12: 30% RVR: 75% SVR12: 50% RVR: 63% SVR12: 50% |
Nausea asthenia | 1 |
| NNI-Site 2 inhibitorsVX-22242 | Vertex | I | 24 | 250 mg BID 500 mg BID 750 mg BID 1500 mg QD |
NNIs 3 days | Mean HCV RNA reduction −3.2 log 10 IU/ml | Diarrhea (25%) Headache (20%) Nausea (12%) |
1 |
| NNI-Site 3 inhibitors Setrobuvir ANA59843 | Anadys | II | 60 | 200 mg BID 400 mg BID |
NNIs + PR 12 w + PR 24/36 w | Naïve G1: RVR: 56% EVR: 73% RVR: 42% EVR: 75% |
Rash | 1 |
| NNI-Site 3 inhibitors ABT-33344 | Abbott | II | 16 | 400 mg BID 800 mg BID |
NNIs 2 days + PR 12 w + PR 36 w | Naïve G1 SVR24: 63% SVR24: 63% |
AE profile similar to PR | 1 |
| NNI-Site 3 inhibitors ABT-07244 | Abbott | II | 23 | 100 mg QD 300 mg QD 600 mg QD |
NNIs + PR 12 w + PR 36 w | Naïve G1: SVR24: 50% SVR24: 25% SVR24: 86% |
AE profile similar to PR | 1 |
| NNI-Site 4 inhibitors Tegobuvir (GS9190)45 | Gilead | II | 252 | 40 mg BID | NNIs + PR 24 w or 48 w | Naïve SVR: 56% | Rash | 1 |
Abbreviations: AE, adverse event; EVR, early virologic response (Week 12); BID, twice daily; HCV, hepatitis C virus; NI, nucleotide inhibitor; NNI, non-nucleoside inhibitor; PR, pegylated–interferon + ribavirin; RBV, ribavirin; RGT, response-guided therapy; QD, once daily; RVR, rapid virologic response (Week 4); SVR, sustained virologic response; SVR12, sustained virologic response at week 12; w, week.