Table 1.
Overview of clinical efficacy of second-wave PIs
| Protease Inhibitor (PI) | Company | Current Clinical Phase | Number of patients | Dose Per Day | Duration of Therapy | Viral Response | Side Effects | Active against HCV Genotype |
|---|---|---|---|---|---|---|---|---|
| Simeprevir TMC-43515,16,96–98 | Tibotec | II | 461 | 150 mg QD | PI + PR 12–24–48 w +PR 24–36 | Null-R G1: SVR: 51% Relapsers G1: SVR: 85% Partial R G1: SVR: 75% |
Anemia 20% Bilirubin increase | 1,2,4,5,6 |
| III | 394 48 cirrhotic |
QUEST-1: PI + PR 12 w +PR 12–36W (RGT) | Naïve G1: SVR: 80% Cirrhosis naïve GT-1 SVR12: 58% |
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| III | 391 32 cirrhotic |
QUEST-2: PI + PR 12 w +PR 12–36W (RGT) | Naïve G1: SVR: 81% Cirrhosis naïve GT1: SVR12: 65% |
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| Faldaprevir BI-201 13517,18 | Boehringer | III | 656 | 120 mg vs 240 | PI 12/24 w + 24/48 w PR | Naïve GT1: SVR: 80% | Rash; jaundice | 1,2 |
| Ingelheim | II | 288 | 240 mg QD | PI + PR 24 w ± 24 w PR | Null-R G1: SVR: 35% Partial R G1: SVR: 50% |
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| Danoprevir ITMN-191, RG 722719,20 | Roche | II | 421 | DAUPHINE: 200/r mg BID 100/r mg BID |
PI/r + PR 24 w | Naïve G1: SVR24: 89% 79% 66% |
Nausea, diarrhea, neutropenia ALT increase | 1,2,4 |
| 29 | 50/r mg BID | G4: SVR12: 100% | ||||||
| 49 | 100/r mg BID | PI/r + PR 24 w | Partial R: SVR 12: 56% G1b 91%, G1a 30% |
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| Vaniprevira MK-700921,22 | Merck | II/III | 94 | Naïve: 300 mg BID 600 mg BID 600 mg QD 800 mg QD |
4w/44 PR | Naïve G1: SVR 61% SVR 80% SVR 78% SVR 84% |
Nausea | 1,2 |
| 211 | Treatment-experienced: 600 mg BID 24 w 600 mg BID 24 w + 24 w PR 600 mg BID 48 w 300 mg BID 48 w |
PI + PR 24 w ± PR 24 PI + PR 48 w |
Trt-experienced Null-R SVR: 71% SVR: 50% SVR: 85% SVR: 80% SVR: 67% SVR: 50% SVR: 78% SVR: 40% |
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| ABT-45023 | Abbott | II | 35 | 100/r or 200/r mg QD | PI + PR 12 w + 12–36 w PR | Naïve G1: SVR12: 88% | AE profile similar to PR | 1 |
| Sovaprevir ACH-162524 | Achillion | II | 64 | 200–800 mg QD | PI + PR 28 d + PR 44 w | Naïve G1: SVR12: 63–86% | AE profile similar to PR | 1 |
| 58 | PI + PR 12 w + 36 PR w | Naïve G1: EOT: 69–100% | ||||||
| Asunaprevir BMS-65003225,26 | BMS | II | 47 | 200–600 mg BID 600 mg BID + Daclatasvir 60 mg QD ± PR 24 w |
PI + PR48 w PI + NS5A inhibitor 24 w PI + NS5A inhibitor + PR 24 w |
Naïve G1: SVR: 83–92% Null-R G1: SVR: 36% SVR: 100% |
AE profile similar to PR | 1,4 |
Abbreviations: AE, adverse event; BID, twice daily; EOT, end of treatment response; HCV, hepatitis C virus; PI, protease inhibitor; PI/r, ritonavir-boosted protease inhibitor; PR, pegylated–interferon + ribavirin; QD, once daily; RBV, ribavirin; RGT, response-guided therapy; RVR, rapid virologic response (Week 4); SVR, sustained virologic response; SVR12, sustained virologic response at week 12; SVR24, sustained virological response at week 24; w, week; /r, ritonavir-boosted; vs, versus.