Table 1. Variants of Interest from a Pooled Analysis of Subjects Who Did Not Achieve an SVR in Phase 2 and 3 Studies.
| NS3 Variant | Replicon IC50 Fold-Changea | Subtype | Treatment-Naïve Occurrence% (n)b | Treatment-Failure Occurrence% (n)c | pd |
| Significant | |||||
| R155K | 5.9 | 1a | 1.21 (27) | 71.4 (372) | <1E-307 |
| V36M | 6.8 | 1a | 0.63 (14) | 63.15 (329) | <1E-307 |
| R155T | 20.0e | 1a | 0.04 (1) | 3.84 (20) | 8.05E-33 |
| V36A | 7.5 | 1a | 0 (0) | 2.69 (14) | 6.82E-11 |
| A156S | 22.4 | 1a | 0 (0) | 1.92 (10) | 5.65E-08 |
| D168N | 0.9 | 1a | 0.04 (1) | 1.15 (6) | 9.52E-08 |
| T54A | 6.3 | 1b | 0 (0) | 28.31 (62) | 8.55E-58 |
| A156S | 9.6 | 1b | 0.07 (1) | 10.96 (24) | 3.95E-44 |
| V36A | 7.4 | 1b | 0 (0) | 16.89 (37) | 7.88E-34 |
| A156T | >62f | 1b | 0 (0) | 7.31 (16) | 1.00E-14 |
| V36M | 7.0 | 1b | 0.07 (1) | 3.65 (8) | 6.60E-12 |
| T54S | 4.2 | 1b | 2.11 (29) | 7.31 (16) | 2.77E-05 |
| Observed but not significant | |||||
| V36G | 11.3 | 1b | 0 (0) | 0.46 (1) | 1.37E-01 |
| V36I | 0.3e | 1a | 0.09 (2) | 0.19 (1) | 3.74E-01 |
| V36I | 0.3 | 1b | 0.29 (4) | 0.91 (2) | 1.34E-01 |
| V36L | 2.2e | 1a | 1.89 (42) | 4.03 (21) | 1.32E-03 |
| V36L | 2.2 | 1b | 0.95 (13) | 2.28 (5) | 6.02E-02 |
| I132V | 1.8 | 1a | 0.54 (12) | 1.54 (8) | 8.35E-03 |
| R155G | 7.4e | 1a | 0 (0) | 0.19 (1) | 1.90E-01 |
| R155M | 5.6e | 1a | 0 (0) | 0.19 (1) | 1.90E-01 |
| A156F | >62f | 1b | 0 (0) | 0.46 (1) | 1.37E-01 |
| A156N | >62f | 1b | 0 (0) | 0.91 (2) | 1.88E-02 |
| A156V | >62f | 1b | 0 (0) | 0.46 (1) | 1.37E-01 |
Replicon IC50 values are the mean from at least three independent experiments with fold-change relative to wild-type (WT) replicon cells. The mean (SD) IC50 value of telaprevir in G1b WT (mADE) replicon cells is 0.482 (0.122) µM (n = 15). In G1a WT replicon the mean (SD) IC50 value of telaprevir is 0.961 (0.132) µM (n = 8).
Numerator is number of subjects that possess the given variant; denominator is total count of subjects that have sequence data available at that position.
Treatment-Failure Occurrence indicates the number of subjects in TPR or T/P containing groups from Phase 2 and 3 studies who did not achieve an SVR that had the given variant at the treatment-failure timepoint. The denominator is the total number of subjects from Phase 2 and 3 studies who did not achieve an SVR with treatment-failure timepoint sequencing data available.
The value tests for enrichment of the variant in the treatment-failure population (Alpha[Bonferroni corrected]: 1a, 0.0000919; 1b, 0.000102).
Was determined in replicon 1b.
The replicon IC50 is greater than 30 µM, the maximum concentration of telaprevir used in the assay.