替诺福韦进入中国早知道V220120917.ppt

* Combined Clinical Summary –Year 6(102; HBeAg- and 103; HBeAg+) Virologic Intention to treat analysis (LTE-TDF): 102 - HBV DNA 400 copies/mL : 81 % (281/345) 103 - HBV DNA 400 copies/mL : 62 % (157/251) On-treatment analysis: 102 - HBV DNA 400 copies/mL : 99.6% (283/284) 103 - HBV DNA 400 copies/mL : 99 % (167/169) Safety Overview 80% of patients entering open label phase remained on the study through year 6 2% of patients discontinued TDF for an AE 7 drug-related SAEs (including 1-mild renal failure [Scr 1.4], 2-osteoporosis, 1-ALT increase) Renal events were uncommon (≤1.5%) No treatment-emergent fractures considered to be related to study drug Serologic HBsAg loss 11% (n=24; Study 103 [KM%]) HBsAg seroconversion 8% (n=18; Study 103 [KM%]) 1 patient had confirmed HBsAg loss/seroconversion at year 5 in Study 102 HBeAg loss 50% (82/163) [on-treatment] HBeAg seroconversion 37% (61/163) [on-treatment] Histology (5 years) Histologic response 87% (304/348) showed histologic improvement Stable fibrosis or regression of fibrosis 96% (335/348) of patient improved or no change Reversal of Cirrhosis (Ishak 5 after cirrhosis at baseline) 74% (71/96) *See following slides for more details Conclusions: TDF demonstrates potent efficacy and a favorable safety profile in treatment-na?ve HBeAg-positive and HBeAg-negative patients through 6 years Resistance No subject developed resistance to TDF *See following slides for more details Biochemical ALT normalization (on-treatment analysis) 102 – 86% (228/265) 103 – 77% (127/162) Summary of Resistance Analyses Through Year 6 For Patients Originally Randomized to TDF or ADV TDF-TDF ADV-TDF *7, 5, 5, and 1 subjects on FTC+TDF at Yrs 3, 4, 5, and 6 Year Number of Subjects Total Subjects Subjects with Viremia Subjects with Confirmed Resistance *4, 1, and 1 subjects on FTC+TDF at Yrs 3, 4, and 5 426 389 (91%) 364 (85%) 348 (82%) 323 (76%) 39 (9%) 24 (6%) 13* (3%) 10* (3%) 9* (3%) 0 0 0 0 0 1 2 3 4 5 0 0 0 0 196 192 (98%) 18