Hepatitis C – BI-201335

Hepatitis C – BI-201335 – 9-May-2012
Source

Abstract

The standard treatment for hepatitis C infection is with an interferon plus the antiviral drug ribavirin; not only does this unpleasant treatment last for many months, only around half of all those who are treated respond, leaving few options if it fails.

The standard treatment for hepatitis C infection is with an interferon plus ribavirin, but only around half of those who are given this unpleasant treatment over many months respond.
Two new antiviral drugs that act by a novel mechanism were approved recently: the NS3/NS4A inhibitors boceprevir and telaprevir. By adding one of these to the standard regimen, the chance of success roughly doubles, and the duration of treatment is shortened. However, both add further side-effects into the mix, and Boehringer Ingelheim is working on a once-daily second-generation oral NS3/NS4A inhibitor, BI-201335, which it hopes will have fewer side-effects than the first generation drugs.¹

In one Phase IIb trial, therapy-naïve patients with genotype 1 HCV infection were given 120 or 240mg of the drug once a day in combination with peginterferon and ribavirin for 24 weeks, either with or without a lead-in period of three days of standard therapy only.² Either way, those given the higher dose and who had a rapid and extended virological response were re-randomised at week 24 either to continue therapy for a further 24 weeks, or stop therapy entirely. This prolongation did not increase the response rate, which was overall in excess of 90% in the higher dose group, whereas the viral breakthrough rate was higher in the lower dose group. The lead-in period made no difference.

A similar Phase IIb trial was carried out in previous non-responders, with doses of 240mg either once or twice a day.³ Again, the lead-in had no effect, and this time there was a difference between those who stopped at 24 weeks and those who continued on the therapy, with sustained virological responses of 40% and 72% respectively. Phase III trials are underway.

BI-201335 is also being investigated without interferon in the drug combination.⁴ A total of 32 treatment-naïve patients with chronic HCV infection were given 120mg of the drug once a day, in combination with either 400 or 600mg of another experimental drug, the NS5B non-nucleoside polymerase BI-207127, and 1000–1200mg of ribavirin a day for four weeks.

In the group given the lower dose of the second drug, a virologic response rate of 73% was seen after four weeks, with a higher response rate in patients with HCV genotype 1b than genotype 1a. In contrast, the higher dose group saw a response rate of 100% after three weeks, which was maintained to four weeks, and there was no difference between the genotypes.

references
1. M. Llinas-Brunet et al. J. Med. Chem. 2010, 53, 6466
2. M.S. Sukowski et al. J. Hepatol. 2011, 54 (Suppl. 1) Abst 60
3. M.S. Su kowski et al. J. Hepatol. 2011, 54 (Suppl. 1), Abst 66
4. S. Zeuzem et al. Gastroenterol. 2011, 141, 2047

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