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BILN 2061: HCV protease inhibitor
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Reported by Jules Levin
Two studies on this protease inhibitor were presented at AASLD in Boston last week. Here are the results of BILN 2061 being studied in genotype 1 and non 1 genotypes. The study in genotype 1 was reported at last year’s AASLD and the results were reported again this year. Future plans for development of this drug seems uncertain but it is my understanding that the developer, Boerhinger Ingleheim, has another HCV protease inhibitor and an HCV polymerase inhibitor in earleier stages of development. Two additional HCV protease inhibitors were reported on at AASLD. VX-950 is being developed by Vertex Pharmaceuticals. In speaking with the company they told me they are planning clinical development to begin in early 2004. Schering Plough is in phase I now with SCH-7, an HCV protease inhibitor and is planning the next phase of studies for 2004.
SAFETY AND ANTIVIRAL EFFECT OF BILN 2061, A NOVEL HCV SERINE PROTEASE INHIBITOR, AFTER ORAL TREATMENT OVER 2 DAYS IN PATIENTS WITH CHRONIC HEPATITIS C, GENOTYPE 1, AND LIVER CIRRHOSIS.
Heiner Wedemeyer and colleagues from Boerhinger Inelheim reported on this study in poster at AASLD. BILN 2061 is a potent and specific inhibitor of the HCV serine protease in-vitro and in patients infected with HCV genotype 1 (GT 1). In previous studies, no safety issues were found in patients with minimal and advanced fibrosis who were treated with BILN 2061 for 2 days. In a first exploratory trial, the effect of a 2-day oral treatment with BILN 2061 was investigated in patients with liver cirrhosis who were infected with HCV GT 1.
In a randomized, double-blind group comparison, 10 patients with HCV GT 1(InnoLiPA) and liver cirrhosis (Child's A) were treated with 200 mg BILN 2061 or placebo (randomized 8:2) given b.i.d. over 2 days in an oral solution. Virus load (VL) was measured as HCV RNA by Cobas Amplicor HCV Monitor v2.0.
Mean age of all 10 patients was 53 +/-9 years, 2 patients were female. 9/10 patients had been previously treated with anti-HCV therapy. All patients completed the study and were followed up for 12 +/-2 days. VL decreased by ≥2 LOG10 units in 8/8 patients treated with 200mg BILN 2061 b.i.d. No VL decrease was observed in the 2 patients given placebo, one being treatment-naïve. After end of treatment, VL returned to baseline levels within 2-7 days.
ALT increased from 69 to 98 IU/mL in 1 BILN 2061-treated patient after 2 days of treatment, all other transaminase levels remained unchanged. Analysis of adverse events, vital signs, routine laboratory and ECG did not reveal relevant drug-induced changes. Tolerability was assessed by the investigators as "good" in all 10 patients.
An oral dose of 200 mg BILN 2061 b.i.d. over 2 days demonstrated strong antiviral activity against HCV GT 1 in patients with liver cirrhosis. No safety issues were identified among the 8 patients treated with BILN 2061.
ANTIVIRAL EFFECT OF BILN 2061 AFTER ORAL TREATMENT OVER 2 DAYS IN PATIENTS WITH CHRONIC HEPATITIS C, NON-GENOTYPE 1.
Markus Reiser and colleagues (Boerhinger Ingleheim) reported study results. BILN 2061 is a potent and specific inhibitor of the HCV serine protease in-vitro and in patients infected with genotype 1 (GT 1) as recently reported. In a first exploratory trial, the effect of a 2-day oral treatment with BILN 2061 was investigated in GT 2 and GT 3 patients with minimal liver fibrosis.
In a randomized, double-blind group comparison, 10 male patients with HCV other than GT 1 (InnoLiPA) and no or minimal liver fibrosis (Ishak 0-2) were administered 500 mg BILN 2061 or placebo in an oral solution (randomized 8:2) b.i.d. over 2 days. Virus load (VL) was measured as HCV RNA by Cobas Amplicor HCV Monitor v2.0.
Mean age of all 10 patients was 37 +/- 7 years. HCV genotypes were GT 2 (3 patients) and GT 3 (7 patients). 9/10 patients were naive for anti-HCV therapy. All patients completed the study and were followed up for 12 +/- 2 days. VL decreased by ≥1 LOG10 unit in 4/8 patients treated with 500mg BILN 2061 b.i.d., without detectable difference between GTs 2 and 3. A weak response was observed in 1 BILN 2061-treated patient, whereas 3/8 BILN 2061-treated patients and 2/2 patients given placebo experienced no response. The largest VL decrease was observed in the one patient with GT 2 HCV that had been previously treated with anti-HCV therapy. However HCV-RNA was still detectable. After end of treatment, VL returned to baseline levels within 1-7 days.
No adverse events were reported. Liver function tests did not change during treatment. Vital signs, routine laboratory and ECG did not show relevant drug-induced changes. Tolerability was rated "good" by the investigators in 9 patients and "satisfactory" in 1 BILN 2061-treated patient.
BILN 2061, given p.o. over 2 days at 500 mg b.i.d., demonstrated antiviral activity in 5/8 non-GT-1 in patients. In contrast to our previous results in GT-1 patients, the antiviral activity was not uniform and less pronounced. No safety issues were identified among the 8 patients exposed to BILN 2061.
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