Sustained viral response achieved in 83% of hepatitis C infected patients with new HCV protease inhibitor from Boehringer Ingelheim

Final results from two clinical Phase IIb studies presented at EASL 2011 demonstrate up to 83% SVR in treatment naïve HCV patients and up to 41% in previously unsuccessfully treated patients, respectively

New data presented today at the International Liver Congress^TM 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.

NOTES TO EDITORS

Additional BI 201335 Studies to be Presented at EASL

• SVR and pharmacokinetics of the HCV protease inhibitor BI 201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV (Poster 1231. S. Pol, et al.)
• Mechanisms of isolated unconjugated hyperbilirubinaemia induced by the HCV NS3/4A protease inhibitor BI 201335 (Poster 1236. R. Sane, et al.)
• BI 201335 pharmacokinetics and early effect on viral load in HCV genotype-1 patients (Poster 1249. C. Yong, et al.)
• Preclinical characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.)

Posters are presented on Saturday, 2 April, 2011, 09:00h - 18:00h.

About Hepatitis C Virus (HCV)

HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.

About Boehringer Ingelheim in Virology

Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral suspension, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.

Boehringer Ingelheim in Hepatitis C Virus (HCV)

BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II programme supports the investigation of BI 201335 in Phase III trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.

For more information, please visit www.boehringer-ingelheim.com

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Contact:

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