Transcript Optimal treatment for CHC G1

How to optimize treatment of
G1 patients?
Prof. G. K. K. Lau 2012
Introduction
• Standard of care (SOC) for chronic HCV infection
– Peginterferon (PegIFN) + ribavirin (RBV)
– 48 weeks (HCV G1, 4, 5 and 6)
– 24 weeks (HCV G2 and 3)
• Induce sustained virologic response (SVR) rates
(associated with long-term clearance of HCV infection)
– 40-50% (G1)
– >80% (G2 and 3)
• Two major advances
– Direct-acting antiviral (DAA) agents
– Single-nucleotide polymorphisms
Prof. G. K. K. Lau 2012
DAA Agents
• Five distinct drug classes currently under development
• The only drugs approved by FDA at present
– Inhibitors of the HCV non-structural protein 3/4A
(NS3/4A) serine protease
– Inhibits HCV replication and virion assembly
• Boceprevir (BOC)
• Telaprevir (TVR)
– Monotherapy: rapid development of drug resistance
– Combination therapies (with PegIFN and RBV) lower
drug resistance and improves antiviral response.
Prof. G. K. K. Lau 2012
Optimal treatment for CHC G1
(Naïve Patients)
• BOC /TVR in combination with PegIFN-α and RBV
have shown great improvement on SVR compared to
SOC
• For Treatment Naïve Patients
– Four weeks lead-in treatment, PegIFN-α and RBV
only; BOC 800 mg (with food), 3 times/day with
PegIFN-α and RBV (24-44 weeks)
– TVR 750 mg (with food), 3 times/day with PegIFN-α
and RBV (12 weeks) + 12-36 weeks of PegIFN and
RBV
Prof. G. K. K. Lau 2012
Optimal treatment for CHC G1
(Naïve Patients)
• Patients without cirrhosis (BOC/PegIFN/RBV treated)
– HCV RNA undetectable at weeks 8 and 24
– Shortened duration of treatment (28 weeks: 4 weeks leadin + 24 weeks of combination therapy)
•
Patients without cirrhosis (TVR/PegIFN/RBV
treated)
–
–
•
HCV RNA undetectable at weeks 4 and 12
Shortened duration of treatment (24 weeks)
Patients with cirrhosis
– 48 weeks therapy regardless of drug use (BOC/TVR
+ PegIFN + RBV)
Prof. G. K. K. Lau 2012
Optimal treatment for CHC G1
(Naïve Patients)
• Treatment termination (patients without cirrhosis)
– HCV RNA level >100 IU/mL at week 12 or detectable
at week 24
• Treatment termination (patients with cirrhosis)
– HCV RNA level >1000 IU/mL at week 4 or 12 and/or
detectable at week 24
Prof. G. K. K. Lau 2012
Optimal treatment for CHC G1
(Patients Previously Received Therapy)
• Virological relapse / partial responders after a
prior course of treatment with PegIFN-α and/or
RBV  Re-treatment with BOC/TVR + PegIFN-α
and/or RBV
• Re-treatment with TVR/PegIFN-α /RBV for prior
null responders to standard PegIFN-α/RBV
therapy
• Response-guided therapy using BOC/TVR
based treatments cannot be recommended for
null responder
Prof. G. K. K. Lau 2012
Optimal treatment for CHC G1
(Patients Previously Received Therapy)
• Treatment termination (BOC/PegIFN alfa/RBV)
– HCV RNA level >100 IU/mL at week 12
– High chance of antiviral resistance development
• Treatment termination (TVR/PegIFN alfa/RBV)
– HCV RNA level >1000 IU/mL at week 4 or 12
– High chance of antiviral resistance development
Prof. G. K. K. Lau 2012
Role of IL28B Testing
• IL28B genotype
– Pretreatment predictor of SVR to PegIFN alfa,
RBV and protease inhibitor therapy (CHC G1)
– Testing for additional information on possible
treatment response or probable treatment
duration needed
Prof. G. K. K. Lau 2012
Other complications
• Adverse events, e.g. Anemia
– Should reduce RBV dose / terminate treatment
• Virological breakthrough (>1 log increase in serum HCV
RNA above nadir)
– Protease inhibitors therapy should be discontinued
• Drug-Drug interactions (affects pharmacokinetic
parameters)
• Patients who: Fail to have virological
response/Experience virological breakthrough/Relapse
on protease inhibitor
– Should not receive re-treatment with other protease
inhibitor
• TVR and BOC are not recommended for patients under
18 years of age (safety and efficacy concerns)
Prof. G. K. K. Lau 2012
Closing Remarks
• BOC and TVR are promising agents for
improved SVR in CHC G1 patients
• BOC/TVR + PegIFN-α/RBV combination
therapies have shown great improvement on
SVR compared to SOC
• Many complex treatment issues remain to be
solved
• Further phase 2 and 3 testing required
– Asian
– Genotype/subtype
Prof. G. K. K. Lau 2012