2006 10 18 2006 12 22 2007 11 14 2007 12 12 2008 05 28 2008 12 11 2010 10 14 2011 02 11 2011 08 04 2012 04 28 2012 12 20 2013 01 14 2014 12 05 2015 03 09 α-2a α α-2a [ ] / [] α-2a Pegasys Peginterferon alfa-2a Solution for Injection Juyierchun Ganraosu alfa-2a Zhusheye α-2a DNA α-2a PEG (10.0 mg/ml) 80 1/27
1. HBsAg HBV DNA 2. HCV HCV RNA 135 μg/ 0.5ml / 180 μg/ 0.5ml / 1. 1.1 180 μg 1 48 1.2 180 μg 1 2 3 800 mg 1 1000-1200 mg 1 HCV 1 48 HCV 2/3 24 1 2/27
1 1 180μg <75 kg=1000mg 75 kg=1200mg 48 48 2/3 180μg 800mg 24 HCV 4 n 66 HCV 1 HCV 5 6 48 12 12 HCV RNA 50 IU/ml 100 copies /ml2log 10 HCV 1 HCV 2/3 96 93 12 HCV 2/3 12 24 12 <5% 2 2 12 1 n=569 2/3 n=96 12 102 97 95% 97/ 102 3 3 100% 3/3 12 467 265 57% 265/467 93 81 87% 81/93 2. / 135μg 90μg 45μg 2.1 3 ANC 750 /mm 3 ANC 500 /mm 3 ANC 1000 /mm 3 90 g 3/27
50,000 /mm 3 90μg 25,000 /mm 3 <10g/dl 8.5g/dl 10 4 2g/dl 600mg/day 200mg 400mg 8.5g/dl 4 12g/dl 600mg/day 800mg/day 3 600mg/day 135/90/45μg <50000/mm 3 <750/mm 3 <500/mm 3 >25000/mm 3 3 <25000/mm <25000/mm 3 - - <10g/dl 8.5 g/dl 4 2g/dl <8.5g/dl 4 <12g/dl 2.2 α ALT ALT 135μg ALT ALT ALT ALT 4/27
3. 3.1 18 3.2 20 ml/min 25%-45% 135μg 180μg 3.3 α-2a 1. - 48 24 6 88% 53% 6% 4% 5% 1% 2. - 2.1 ALT HCV ALT HCV ALT 24 48 4 180μg + 800mg 24 180μg + 1000/1200mg 48 3% 11% 4% 10% 1% 3% 19% 39% 5/27
- 1145-17 1/3 48 91% 60% 64% 56% 47% 45%7 48 1 2 48 z 2 64 2 60 54 2 56 4323/53 15% 2513/53 15% 2 166/38 15% 114/38 15% 5521/38 6 2 6 2 15% 6 5 5% α- 2a 180 μg x /1.73m 2 + 15mg/kg 48 NV17424 N=55 % 91 45 33 6/27
29 20 5 5 64 5 60 18 18 9 7 5 56 7 7 5 5 47 20 15 11 36 15 13 13 7 7/27
7 48 24 48 6 24 48 10% 610% * ** WV16240 NV15801 + NV15942 NV15801 + NR16071 NV15801 + NV15489 + NV15942 WV16241 NV15495 + NV15496 + NV15497 α- α- 2a α- 2a α- 2a α- 2a α- 2a α- 2a 2b 3 MIU 180μg 180μg 180μg 180μg 180μg 180μg + 48 48 + + + + 1000 - n=448 n=827 800mg 1000-1200 800mg 800mg 1200mg 24 mg 24 48 48 n=207 48 n=212 n=210 n=443 n=887 % % % % % % % 21 49 45 49 51 51 53 52 35 37 39 30 43 54 6 30 30 25 24 25 34 7 22 28 21 16 16 15 11 7 18 15 22 23 16 1 11 9 10 4 3 9 2 5 9 7 12 13 6 6 24 29 28 32 40 28 8/27
6 16 15 14 19 26 10 4 15 9 10 9 12 9 2 1 2 6 9 10 5 13 16 20 27 16 13 26 4 5 2 7 7 9 10 25 37 42 38 38 44 49 10 26 20 22 32 30 23 23 52 48 47 44 56 49 6 20 30 32 35 36 37 3 17 28 24 27 26 27 4*** 18 17 21 26 27 28 6 14 13 15 8 17 14 2 9 8 10 9 5 13 3 6 8 8 10 8 12 1 5 11 13 14 15 14 2 4 8 13 14 19 7 17 22 25 24 20 28 33 6 12 25 21 16 20 18 <1 9 15 16 <1 2 13 1 5 13 12 11 9 13 4 6 7 9 14 16 5 9/27
<1 - <1 1 9 10 <1 * 450 ** *** 10%2% HIV-HCV HIV-HCV 1% <10% 1 2 3 4 5 6 7 8 9 10 11 12 13 1%2% HCV/HIV / 10/27
α ALT ALT 180μg 1000/1200mg 48 2% 11/887 1.7% 14/827 4-8 1.99-0.75 10 9 /L 99-50 10 9 /L 180μg 1000/1200mg 48 0.749-0.5 10 9 /L<0.5 10 9 /L 24% 216/887 5% 41/887 1-5% II NV1603713% 6/46 180μg / NV15801 4.9% 11/27
Stevens Johnson PRCA α α- Child-Pugh 6 HIV-HCV atazanavir indinavir 3 6 1. CNS 12/27
2. α- 3. ALT ALT ALT HBV 10 4. 5. α- 6. α α- 7. / α- 8. 1500 /mm 3 75,000 /mm 3 13/27
10g/dl 3 7 HCV 4 6 9. 10. α- 11. α- 12. α- 20 13. 14. HCV/HIV HIV HAART HAART HAART 14/27
Child-Pugh 7 Child-Pugh 15. 5 17 48 2 16 15 11 15 5 6 2 15 - - HCV 16. 24 HCV RNA<50IU/ml 17. 1 90,000 /mm 3 2 ANC1,500 /mm 3 3 TSH T4 2 4 4 WBCANC WBC ANC ANC 15/27
180μg 1000/1200 mg 48 13% 180μg 800 mg 24 3%<10 g/dl 4 α- TSH TSH TSH TSH 16/27
6 2 18 180μg 1 4 P450 3A4 2C9 2C19 2D6 AUC P450 1A2 25% P450 1A2 4 17/27
III 1 α-2a 180 µg 600 mg α 6-6-MTIMP 2 1260μg/ 540μg/ 630μg/ 1. 1.1 III HBeAg WV16240 HBeAg WV16241 1351 180 g 1 HBV DNA ALT WV16240 814 HBeAg WV16241 537 HBeAg HBe 48 24 HBV/HIV HBeAg HBeAg 3 4 18/27
* * Metavir Knodell 7 HBV DNA COBAS AMPLICOR HBV 200 copies/ml 7 HBeAg WV16240 180μg+ 180μg+ 100mg (n=271 100mg (n=272 (n=271) HBeAg / HBeAb WV16241 180μg+ 180μg+ 100mg (n=177 100mg (n=181) (n=179) HBeAg 32% 1 27% 19% HBV DNA* ALT 32% 2 34% 22% 43% 5 44% 29% 41% 3 39% 28% 59% 6 60% 44% HBsAg 3% 4 3% 0% 3% 2% 0% * HBeAg HBV DNA<10 5 copies/ml HBeAg /HBe HBV DNA<2 10 4 copies/ml 1 95% =2.00 1.34-2.97p <0.001 Cochran-Mantel-Haenszel 2 95% =1.64 1.12-2.42p =0.012 Cochran-Mantel-Haenszel 3 95% =1.77 1.23-2.54p =0.002 Cochran-Mantel-Haenszel 4 ρ =0.004 Cochran-Mantel-Haenszel 5 95% =1.84 1.17-2.89p =0.007 Cochran-Mantel-Haenszel 6 95% =1.86 1.22-2.85p =0.004 Cochran-Mantel-Haenszel 1.2 40%HBeAg WV16240 HBeAg WV16241 587 48 24 19/27
HBeAg 354 HBeAg 233 HBVDNA HBeAg ALT HBsAg HBsAg HBeAg /HBeAg HBeAg 2. 2.1 NV15801 NV15942 2405 NV15801 1149 1121 12/465 α-2b 13/457 1121 1 180μg 1 + n=224 180μg 1 + 1000/1200 mg/dayn=453 α-2b 3MIU 3 + 1000/1200 mg/dayn=444 α-2b 8 NV15801 1 2/3 α-2b 43% 24 8 NV15801 n= PEG-IFNα-2a PEG-IFNα-2a IFN α-2b n=224 n=453 n=444 29% 54% 45% 1 1 20% 45% 36% 46% 72% 60% COBAS AMPLICOR TM HCV 2 100copies/ml 50 IU/ml HCV RNA NV15942 1284 24 48 20/27
180μg 1 + 800mg/day 24 n=207 180μg 1 + 1000/1200mg/day 24 n=280 180μg 1 + 800mg/day 48 n=361 180μg 1 + 1000/1200mg/day 48 n=436 NV15942 9 9 NV15942 * NV15942 180μg+ 1000/1200mg n=436 48 63%** 59%*** * 75% 18% 7% ** 12 24 HCV RNA HCV RNA COBAS AMPLICOR TM HCV 2 100copies/ml 50 IU/ml *** 2 21 HCV RNA HCV RNA COBAS AMPLICOR TM HCV 2 100 copies/ml 50 IU/ml 10 NV15942 10 NV15942* 180μg 180μg 180μg 180μg + 800mg + + 800 mg + 24 1000/1200 mg 48 1000/1200 mg 24 48 1 29% 29/101 42% 49/118 41% 102/250 52% 142/271 41% 21/51 52% 37/71 55% 33/60 65% 55/85 16% 8/50 26% 12/47 36% 69/190 47% 87/186 21/27
2/3 84% 81/96 81% 117/144 79% 78/99 80% 123/153 85% 29/34 83% 39/47 88% 29/33 77% 37/48 84% 52/62 80% 78/97 74% 49/66 82% 86/105 4 0% 0/5 67% 8/12 63% 5/8 82% 9/11 * 12 24 HCV RNA HCV RNA COBAS AMPLICOR TM HCV 2 100 copies/ml 50 IU/ml ALT HCV RNA ALT ALT 2.2 ALT HCV 11 NR16071 ALT HCV 180μg/week 800mg/day 24 48 72 NV15942 NR16071 48 52% 24 30% p<0.001p<0.001 HCV 1 48 40% 24 13% 4.47 95% 2.47 8.08 p<0.001 2/3 24 72% 48 78% 1.40 95% 0.59 3.30 p 0.452 11 NR16071 180μg& 800 mg 24 180μg& 800 mg 48 1 * 13% 19/144 40% 57/141 0% 2/3 72% 42/58 78% 46/59 0% * NR16071 1 1000 1200 mg/day 2.3 22/27
12 12 HCV RNA 99% NV15801 NV15942 12 95% 12 66% 12 776 514 2.4 1130 48 24 180μg 34% 28-39% α-2a 3 MIU / 6 MIU 15% 11-19% 29% α-2a 6% 58 63% Knodell 2 α-2a 45% 54% α-2a 31% α-2a α-2a 4 4/1831 90μg 1/96 456 3 180 3/87=3.4% 3 1 397 1 549 1 81 2 α-2a PEG α-2a α α- 23/27
α- 40KD PEG PEG 180μg 3~6 2 5-2 5-OAS 2 5-OAS 1 3 18 MIU 62 180μg 2 5-OAS 25% 20-40 ml/min 90μg 2 5-OAS 40-100 ml/min AUC C max 180μg HCV RNA 24-36 4-16 α- 180μg α-2a 1. PEG α-2a 17β-α- 2a 25 10 6 // 5 α- 2a 2. 1. 180μg 3~6 24 80% 72~96 AUC 1743 459 ng h/ml C max 14 2.5 ng/ml 61-84% α- 24/27
2a Vd 8~14 α 100 60-80 α 3~4 50~130 6~8 2~3 8 48 1.5~2.0 168 2. 23 100 ml/min 20 ml/min >20 ml/min 25-40% 135μg 180μg 62 180μg 115 82 AUC 1663 1295 ng h/ml 9.1 10.3 ng/ml 25/27
Child-Pugh A 2-8 1 / 36 135 μg/0.5 ml/js20140008 180 μg/0.5 ml/js20140009 135 μg/ 0.5 ml/s20120047 S20120048 180 μg/ 0.5 ml/s20120049 S20120050 135 μg/ 0.5 ml/ J20120074 180 μg/ 0.5 ml/ J20120075 Roche Pharma (Schweiz) Ltd. Schoenmattstrasse 2, 4153 Reinach, Switzerland F. Hoffmann - La Roche Ltd. 26/27
Grenzacherstrasse 124, 4070 Basel, Switzerland 1100 201203 (021)28922888 (021)50801800 400-820-6867 www.roche.com.cn 27/27