New data presented today at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), in Berlin, highlighted the efficacy of Boehringer Ingelheim's once-daily oral protease inhibitor BI 201335, in both treatment-naïve and -experienced patients with chronic genotype-1 hepatitis C virus (HCV) infection. Genotype-1 HCV is the most challenging genotype of HCV to treat.

Results from SILEN-C1 trial show high rates of sustained viral response (SVR, which is considered viral cure) in patients with no previous treatments, who received either 120mg or 240mg BI 201335 once-daily plus the current standard-of-care (SOC), i.e. pegylated interferon (PegIFN) and ribavirin (RBV). Up to 87% of patients were able to shorten overall treatment duration from 48 to 24 weeks.

In the SILEN-C2 trial, in non-responding patients, the 240mg dose of BI 201335 once daily also achieved impressive results in a population that has not responded to SOC, and achieved such without a lead in therapy.

"The final results from the SILEN-C1 and 2 trials have demonstrated the high potential for excellent efficacy of this once daily protease inhibitor in a broad range of HCV patients," said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. "The current standard-of-care in HCV is not effective for many patients. The viral cure rates achieved by protease inhibitors such as BI 201335 highlight the possibility to improve treatment outcomes as well as the option to shorten the overall treatment duration for the majority of HCV patients."

"Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients," continued Professor Klaus Dugi. "BI 201335 is part of our robust HCV portfolio that we are investigating with the goal of improving current treatment and ultimately paving a path for a simpler, more effective and better tolerated HCV therapy."

Study Details:

(Oral Presentation at EASL, Parallel Session: HCV Drug Development, 16:00h-16:15h, Abstract 60) SILEN-C1: Sustained Virologic Response (SVR) and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve Patients with Chronic Genotype-1 HCV Infection The Phase II SILEN-C1 study results show BI 201335 to have strong antiviral activity, with overall SVR rates reaching 83% in the 240mg once-daily group (plus current SOC). Of the patients achieving extended rapid viral response (eRVR, defined as plasma viral load less than 25 IU/ml at week 4 and undetectable at weeks 8-20), 93% achieved SVR with 24 weeks of SOC (PegIFN/RBV) treatment.

In addition to high efficacy at all dose levels, BI 201335 once daily with SOC also demonstrated good tolerability and safety:

The most frequent dose-dependent adverse events in BI 201335 treatment groups were mild gastrointestinal disorders, mild rash or photosensitivity and jaundice resulting from isolated unconjugated hyperbilirubinaemia. Average alanine aminotransferase (ALT) improved in all BI 201335 groups compared to placebo. Of note, there was no excess anaemia reported in the active groups compared to SOC. Phase III trials of BI 201335 are in preparation.

(Oral Presentation at EASL Parallel Session: HCV Drug Development, 17:30h-17:45h, Abstract 66) SILEN-C2: Sustained Virologic Response and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Chronic HCV Genotype-1 Patients with Non-Response to PegIFN/RBV

The Phase II SILEN-C2 study evaluated the virological response and safety of different doses of BI 201335 in treatment-experienced patients who did not respond to at least 12 weeks of prior treatment with PegIFN/RBV. The results demonstrate that treatment with BI 201335 once daily at 240mg, plus SOC provides high efficacy and good tolerability in this very difficult-to-treat patient population, with 41% achieving SVR. As is seen in SILEN-C1, a 3-day lead in with SOC was associated with decreased viral response. Phase III trials of BI 201335 are in preparation.

The most frequent dose-dependent adverse events in BI 201335 treatment groups were similar to those seen in SILEN-C1. Serious or severe adverse events were reported more frequently in the BI 201335 240mg BID with lead in (LI) group.

Source
International Liver Congress