“Strong reasons make strong actions” — The antiviral efficacy of NS3/4A protease inhibitors


  • Conflict of interest: Nothing to report.



Novel, potent and well-tolerated hepatitis C (HCV) drugs are still needed. BILN 2061 is a potent and specific inhibitor of HCV serine protease in vitro. Pre-clinical toxicology data and studies in healthy volunteers supported the administration of BILN 2061 to patients with HCV infection.


The antiviral efficacy, pharmacokinetics and tolerability of 25, 200 and 500 mg bid BILN 2061 given as monotherapy for two days in 31 patients infected with chronic genotype 1 HCV infection and with minimal liver fibrosis (Ishak score 0-2) were assessed in a placebo controlled double blind pilot study. In two, subsequent, placebo controlled studies of similar design, 200 mg bid BILN 2061 was administered for two days to 10 patients with advanced liver fibrosis (Ishak score 3-4) and to 10 patients with compensated cirrhosis (Ishak 5-6).


Viral RNA reductions of 2-3 log10 copies/mL were achieved in most of the patients. There was a trend towards a higher number of patients receiving 500 mg BILN 2061 achieving a viral RNA reduction >3 log10 copies/mL as compared to patients receiving 25 mg BILN 2061. Advanced fibrosis or compensated cirrhosis did not affect the antiviral efficacy of BILN 2061. BILN 2061 was well tolerated in all studies.


BILN 2061 is a well tolerated and very active compound, which reduced serum viral RNA concentrations after two days of treatment in patients infected with genotype 1 HCV independent from the degree of fibrosis. Nevertheless further clinical trials are on hold pending resolution of animal toxicity issues.