Advances in antiviral therapy for chronic hepatitis C

Transcript

1 HCV R A Advances in antiviral therapy for chronic hepatitis C ZHUO Hong WANG Tao XIE Song-mei CHEN Ying Center for Drug Evaluation China Food and Drug Administration Beijing China AbstractNon-Anon-B post-transfusion hepatitis was proposed in the 1970sbut until 1989hepatitis C virus HCV was identified and confirmed as the main pathogenic factor of post transfusion hepatitis by application of modern molecular cloning technologies. Compared with hepatitis Bhepatitis C is not only liable to become chronical andeasier to progress to cirrhosis and hepatocellular carcinoma HCC but also more difficult to treat. Moreover there is no effective vaccine for HCV. Thereforehepatitis C is one of the major public health problems in the world. With the advancing of research and understanding of hepatitis C virus the research and development of drugs directly agaist HCV are currently close to a breakthrough. At presentmany new drugs with multiple mechanisms have been approvedand more and more others candidates are entering clinical trials. This article reviews the epidemiology and therapy about HCVand offers information on drugs currently under investigation and drugs already on the market. Key wordschronic hepatitis C hepatitis C virus antiviral therapy drug research and development 1 2c HCV 3a HCV Flaviviridae RNA HCV 6 3e 3f HCV 4 HCV HCV 5 HCV 6 1 HCV 1a HCV 1b 2a HCV 1b 1b 80% 1b HCV 1c HCV 2a 1b 2a Zhuoh@ cde. org. cn Cheny@ cde. org. cn HCV 3b HCV 3c 3d CHC

2 HCV 1 HCV SOC 2-3 SOC HCV PEGαIFN 3. 2% 5 HCV 0. 29% ~ 9. 6% 6 HCV 25 ~ 30 5% ~ 25% HCV 10 30% 1% ~ 3% 2 PEGαIFN HCV specifically targeted antivi- RBV CHC ral therapy for HCV STAT-C SOC IFNs HCV RBV IFN HCV CHC HCV 2 /3 1 HCV 24 SVR 42% ~ 46% 2 /3 SVR 76% ~ 82% NS4B RNA 50% 1 40% 4 NS5A RNA RNA NS5B SVR SOC 2 NS2 /3 NS3 NS2 /3 1 4 NS2 /3 NS3 NS3 /4A NS4A /B NS4B /5A SOC NS5A /B NS4B NS3 HCV NS3 /4A 7-8 NS5A NS5B DAA 1 4 ~ 6 SOC SOC HCV HCV HIV 3 SOC DAA SOC SOC 4 SOC 3. 2 NS2 NS3 NS4A DAA boceprevir Victrelis telaprevir Incivek simepre- HIV HBV vir Olysio sofosbuvir Sovaldi

3 4. 1 boceprevir 2011 HCV NS3 /4A 4 α α 1 Victrelis 800 mg po tid 7 ~ 9 h 1 TW HCV-RNA Victrelis RGT α 1 RGT α 4 1 ~ 4 1 RGT a HCV-RNA b α α a 8 HCV-RNA IU ml HCV-RNA 100 IU ml HCV-RNA b Roche COBAS TaqMan HCV-RNA 25 IU ml IU ml α 44 Victrelis 800 mg po tid 7 ~ 9 h mg α 4. 2 telaprevir 2011 HCV NS3 /4A bid 10 ~ 14 h α In- civek α HCV-RNA 1 CHC 2 10 daclatasvir /asunaprevir dual ledipasvir /sofosbuvir 9 2 HCV-RNA a b c / IU ml a Roche COBAS TaqMan HCV-RNA 25 IU ml IU ml - 1 b Incivek α c α

4 4 12 SJS HCV-RNA HCV-RNA IN- CIVEK 4 12 HCV-RNA 36 α 4. 3 simeprevir 2013 HCV NS3 /4A 48 α 150 mg po qd 3 - Stevens Johnson syndrome 2HCV-RNA drug reaction with eosinophilia and systemic symptoms DRESS toxic epidermal necrolysis TEN Olysio + α + α HCV RNA 25 IU ml HCV RNA 25 IU ml HCV RNA 25 IU ml - 1 Olysio α α Olysio 12 α 4. 4 sofosbuvir 2013 NS5B HCV α 4. 5 daclatasvir asunaprevir asu- 400 mg po qd naprevir daclatasvir CHC 1 4 Sovaldi + α a b Sovaldi b Sovaldi b + 24 a 1 4 CHC α b < 75 kg = mg 75 kg = mg 2 CrCl 50 ml min - 1 Sovaldi 24 po daclatasvir 60 mg qd 12 1 CHC NS3 /4A daclatasvir sofosbuvir 24 Sovaldi IL28B CC / HCV NS3 /4A HCV NS5A HCV HCV /HCV /HIV-1 1 SOVALDI po asunaprevir 100 mg bid daclatasvir 60 mg qd 24 daclatasvir asunaprevir 4. 6 daclatasvir sofosbuvir 2014 daclatasvir sofosbuvir SOC 1 4

5 daclatasvir sofosbuvir mg po qd < 75 kg = mg 75 kg = mg HCV RNA 4. 7 daclatasvir SOC daclatavir daclatavir α α 4 daclatasvir HCV RNA 4 HCV RNA > IU ml HCV RNA 25 IU ml HCV RNA 25 IU ml daclatavir α daclatavir α α daclatavir ledipasvir /sofosbuvir 2014 sofosbuvir NS5B ledipasvir NS5A 1 and HBV infection in northern ChinaJ. Gastroenterologia Ja- po 1 qd 12 α + HCV ponica + α J J docs / label /2014 /202258s015lbl. pdf. docs / label /2013 /201917s012lbl. pdf. 1World Health Organization WHO. Hepatitis CEB /OL http / /www. who. int /mediacentre /factsheets / fs164 /en /. 2FREEMAN RBSTEFFICK DEGUIDINGER MKet al. Liver and intestine transplantation in the United States J. Am J Transplant Pt DAVILA JA MORGAN RO SHAIB Y et al. Hepatitis C Infection and the increasing incidence of hepatocellular carcinoma a population-based studyj. Gastroenterology TAO QM WANG Y WANG H et al. Seroepidemiology of HCV Suppl 3 S156 - S158. 5Expert Committee on Chronic Hepatitis C Antiviral Therapy. Expert consensus for antiviral therapy for chronic hepatitis CJ. Chin J ExpClin Infect Dis Electronic Edition J FDA. Label approved on 07 /28 /2014 for VICTRELISEB /OL http / /www. accessdata. fda. gov /drugsatfda_ 10FDA. Label approved on 10 /28 /2013 for INCIVEKEB /OL http / /www. accessdata. fda. gov /drugsatfda_ 11FDA. Label approved on 11 /05 /2013 for OLYSIOEB /OL http / /www. accessdata. fda. gov /drugsatfda _docs / label /2014 /205123s002lbledt. pdf. 12FDA. Label approved on 11 /14 /2014 for SOVALDIEB /OL http / /www. accessdata. fda. gov /drugsatfda_ docs / label /2014 /204671s001lbl. pdf. 13EMEA. EPAR-Product Information 10 /03 /2014 for Daklinza. EB /OL http / /www. ema. europa. eu / docs /en_ GB /document _ library /EPAR _-_ Product _ Information / human / / WC pdf. 14FDA. Label approved on 10 /10 /2014 for HarvoniEB /OL http / /www. accessdata. fda. gov /drugsatfda _docs / label /2014 /205834s000lbl. pdf. /