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 2016 9 27 2016 12 19 2017 05 04 2017 08 16 α-2a α α-2a [ 1/42
] / 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. HBsAg HBV DNA 2/42
2. HCV HCV RNA 135 μg/ 0.5 ml / 180 μg/ 0.5 ml / 1. 1.1 180 μg 1 48 1.2 180 μg 1 2 3 800 mg 1 1000-1200 mg 1 3/42
HCV 1 48 HCV 2/3 24 1 1 1 180μg <75kg=1000mg 75kg=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 /ml2log10 HCV 1 HCV 2/3 96 93 12 HCV 2/3 12 24 12 <5% 2 2 12 12 12 1 102 97 95% 467 265 57% 265/467 4/42
n=569 97/102 2/3 n=96 3 3 100% 3/3 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 μg 50,000 /mm 3 90μg 25,000 /mm 3 <10 g/dl 8.5 g/dl 4 2 g/dl 600 mg/day 200 mg 400 mg 8.5g/dl 4 12 g/dl 600 mg/day 800 mg/day 1000mg 1200mg 3 135/90/45μg 600mg/day 5/42
<750/mm 3 <500/mm 3 <50000/mm 3 >25000/mm 3 <25000/mm 3 <25000/mm 3 - <10g/dl 8.5 g/dl <8.5g/dl - 4 2g/dl 4 <12g/dl 2.2 α ALT ALT 135μg ALT ALT ALT ALT 3 3.1 18 3.2 30 ml/min 6/42
135μg, 135μg, 3.3 α-2a α-α- 1. 48 24 6 88% 53% 6% 4% 5% 1% 2. 2.1 ALT HCV ALT HCV ALT 24 48 1000/1200 mg 48 5% 13% 7/42
1% 3% 1000/1200 mg 48 800 mg 24 11% 3% 39% 19% 4 4 180μg + 800mg 24 180μg + 1000/1200mg 48 3% 11% 4% 10% 1% 3% 19% 39% 2.2-1145-17 1/3 48 91% 60% 64% 56%47% 45%7 48 1 2 5 48 z 2 64 2 8/42
60 54 2 56 43 23/53 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 /1.73m 2 + 15mg/kg 48 NV17424 N=55 % 91 45 33 29 20 5 5 9/42
64 5 60 18 18 9 7 5 56 7 7 5 5 47 20 15 11 10/42
36 15 13 13 7 7 48 24 48 2.3 α-2b 72 48 72 12% 13% 48 6% 7% 72 13% 15% 48 6% 6% Ishak 3 6 50000 / mm 3 48 / 20 10g/dL 26.3% ANC 750 / mm 3 30% 50000 / mm 3 13% 2.4 HIV-HCV 11/42
HIV-HCV CD4+ 200 µl N = 51 NR15961 800mg 48 16% 15% 4% 3% 39% 37% 21% 17% CD4+ CD4+ CD4+ HIV 6 10% 12/42
610% HIV-HCV -2b * NV15801 ** NV15801 + NV15489 + NV15942 NV15801 + NV15942 NR16071 NV15961 MV17150 WV16240 + WV16241 NV15495 + NV15496 + NV15497 α- 2a 180μg 48 n=448 α- 2a 180μg 48 n=827 α- 2a 180μg + 800mg 24 α- 2a 180μg + 1000-1200mg α- 2a 180μg + 800mg 24 α- 2a 180μg + 800mg 48 α- 2b 3 MIU + 1000-1200mg 48 n=443 180μg + 800mg 48 n=288 180μg + 1000mg 1200mg 72 n=156 n=207 48 n=212 n=210 13/42
n=887 % % % % % % % % % 21 49 45 49 51 51 53 40 36 52 35 37 39 30 43 54 41 20 6 30 30 25 24 25 34 16 12 7 22 28 21 16 16 15 10 12 11 7 18 15 22 23 16 26 30 1 11 9 10 4 3 9 6 6 2 5 9 7 12 13 6 - - 6 24 29 28 32 40 28 24 24 14/42
6 16 15 14 19 26 10 16 13 4 15 9 10 9 12 9 7 9 2 1 2 6 9 10 5 - - 13 16 20 27 16 13 26 23 15 4 5 2 7 7 9 10 16 9 25 37 42 38 38 44 49 32 22 10 26 20 22 32 30 23 16 15 15/42
23 52 48 47 44 56 49 35 32 6 20 30 32 35 36 37 19 29 3 17 28 24 27 26 27 15 17 4*** 18 17 21 26 27 28 22 16 6 14 13 15 8 17 14 7 10 2 9 8 10 9 5 13 2 5 3 6 8 8 10 8 12 8 6 1 5 11 13 14 15 14 7 11 2 4 8 13 14 19 7 3 17 16/42
17 22 25 24 20 28 33 10 18 6 12 25 21 16 20 18 5 22 <1 9 15 16 <1 2 13 1 1 1 5 13 12 11 9 13 4 17 4 6 7 9 14 16 5 - - <1 - <1 1 9 10 <1 - - * 450 ** *** 10%2% 17/42
HIV-HCV HIV-HCV 1% <10% 1) 2 3 4 5 6 7 8 9 10 11 12 13 14 1%2% HCV/HIV / 18/42
- α 4-8 HIV-HCV 1% 10% 1000mg/120mg 48 HIV-HCV 7% 14% 10g/dL WBC ANC 4% 5% ANC 500 /mm 3 HIV-HCV 13% 11% ANC 500 / mm 3 5% 50000 / mm 3 75000 / mm 3 19/42
14% 50000 / mm 3 HIV-HCV 10% 8% 50000 /mm 3 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 NV15801 4.9% ALT ALT 180μg 1000/1200mg 48 2% 11/887 1.7% 14/827 1-5% II NV1603713% 6/46 180μg Stevens Johnson PRCA 20/42
α α- Child-Pugh 6 HIV-HCV atazanavir indinavir 3 6 1. 21/42
2. α- 6 3. ALT ALT ALT HBV 10 4. 5. α- 6. 22/42
α α- 7. / α- TSH TSH TSH TSH α- 8. WBC ANC 4 8 ANC 180μg 1000/1200 mg 48 13% 180μg 800 mg 24 3%<10 g/dl 4 1500 /mm 3 75,000 /mm 3 10g/dl 23/42
3~7 HCV 4~6 9. / 10. α- 11. α- 12. 13. HCV/HIV 24/42
HIV HAART HAART HIV HAART α- Child-Pugh 7Child-Pugh 14. 5 17 48 2 16 15 11 15 5 6 2 15 - - HCV 15. 24 HCV RNA<50IU/ml 16. 25/42
2 4 4 4 1 90,000 /mm 3 12g/dL 2 ANC1,500 /mm 3 3 TSH T4 17. 20 26/42
6 2 / 27/42
18 Child-Pugh A Child-Pugh B / C Child-Pugh 5-6, 7-9 10-15 A B C 7 7. mg/dl 1~2 3~4 <2 2-3 >3 1 2 3 1 2 3 1 2 3 28/42
umol/l <34 34-51 >51 1 2 3 g/dl >3.5 3.5-2.8 <2.8 1 2 3 <1.7 1.7-2.3 >2.3 1 2 3 * Trey, Burns and Saunders (1966) 135 g, 135 g, 180μg 1 4 P450 3A4 2C9 2C19 2D6 AUC P450 1A2 25% P450 1A2 4 29/42
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 30/42
48 24 HBV/HIV HBeAg HBeAg 3 4 * * Metavir Knodell 8 HBV DNA COBAS AMPLICOR HBV 200 copies/ml 8 HBeAg WV16240 HBeAg / HBeAb WV16241 180μg+ 180μg+ 100mg 180μg+ 180μg+ 100mg 100mg n=272 100mg n=181 n=271 n=271 n=177 n=179 HBeAg HBV DNA* 32% 1 27% 19% 32% 2 34% 22% 43% 5 44% 29% ALT 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 31/42
3 95% =1.77 1.23-2.54p =0.002 Cochran-Mantel-Haenszel 4 p =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 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 32/42
180μg 1 + n=224 180μg 1 + 1000/1200 mg/dayn=453 α-2b 3 MIU 3 + 1000/1200 mg/dayn=444 α-2b 9 NV15801 1 2/3 α-2b 43% 24 9 NV15801 n= PEG-IFNα-2a PEG-IFNα-2a IFN α-2b n=224 n=453 n=444 29% 54% 45% 1 20% 45% 36% 1 46% 72% 60% COBAS AMPLICOR TM HCV 2 100copies/ml 50IU/ml HCV RNA NV15942 1284 24 48 180μg 1 + 800mg/day 24 n=207 180μg 1 + 1000/1200mg/day 24 n=280 33/42
180μg 1 + 800mg/day 48 n=361 180μg 1 + 1000/1200mg/day 48 n=436 NV15942 10 10 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 11 NV15942 11 NV15942* 180μg 180μg 180μg 180μg 34/42
+ 800mg + + 800mg + 24 1000/1200 mg 48 1000/1200 mg 24 48 1 29% 29/101 42% 49/118 41% 52% 41% 21/51 52% 37/71 102/250 142/271 16% 8/50 26% 12/47 55% 33/60 65% 55/85 36% 69/190 47% 87/186 2/3 84% 81/96 81% 79% 78/99 80% 85% 29/34 117/144 88% 29/33 123/153 84% 52/62 83% 39/47 74% 49/66 77% 37/48 4 0% 0/5 80% 78/97 63% 5/8 82% 86/105 67% 8/12 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 12 NR16071 ALT HCV 180μg/week 800mg/day 24 48 72 NV15942 35/42
NR16071 48 52% 24 30% p<0.001 p<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 12 NR16071 180μg& 800mg 24 180μg& 800mg 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 12 12 HCV RNA 99% NV15801 NV15942 12 95% 12 66% 12 776 514 2.4 1130 48 24 36/42
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- α- 40KD PEG PEG 37/42
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 Cmax 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. 38/42
180μg 3~6 24 80% 72~96 AUC 1743 459 ng h/ml Cmax 14 2.5 ng/ml 61-84% α-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. 50 30~50ml/min 30ml/min ESRD 39/42
180μg α-2a 180μg 60% α-2a 135μg 18 ESRD 135μg α-2a 34% ESRD 62 180μg 115 82 AUC 1663 1295 ng h/ml 9.1 10.3 ng/ml Child-Pugh A 2-8 40/42
1 / 48 JS20130081 135 μg/ 0.5 ml/s20150054 S20150055 180 μg/ 0.5 ml/s20150056 S20150057 135 g/ 0.5 ml/ J20160076 180 g/ 0.5 ml/ J20160077 Roche Registration Ltd. Kingdom 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United 41/42
F. Hoffmann - La Roche Ltd. Wurmisweg, 4303 Kaiseraugst, Switzerland 1100 201203 (021)28922888 (021)50801800 800-820-8780 400-820-8780 9:00-18:00 www.roche.com.cn 42/42