ÿþ<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" "http://www.w3.org/TR/html4/loose.dtd"> <html> <head> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> <title>EASL 2010 - Oral Presentations</title> <link rel="stylesheet" type="text/css" href="style.css"> </head> <body> <table width="750" align="center" border="0" cellspacing="0" cellpadding="0" class="MainTable"> <tr> <td><img src="http://www2.kenes.com/liver-congress2010/PublishingImages/top_ei.jpg" width="760" height="129" /></td> </tr> <tr> <td class="content"><h1>Oral Presentations</h1> <P><b>Session Title:</b> Parallel Session: LATE-BREAKERS<br><b>Presentation Date:</b> Apr 17, 2010</P><h2 align='left'><B>SILEN-C2: EARLY ANTIVIRAL ACTIVITY AND SAFETY OF BI 201335 COMBINED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN (PEGIFN/RBV) IN CHRONIC HCV GENOTYPE-1 PATIENTS WITH NON-RESPONSE TO PEGIFN/RBV</B></h2> <p align='left'><b>M. Sulkowski</b><sup>1</sup>, M. Bourliere<sup>2</sup>, J.-P. Bronowicki<sup>3</sup>, A. Streinu-Cercel<sup>4</sup>, L. Preotescu<sup>4</sup>, T. Asselah<sup>5</sup>, J.-M. Pawlotsky<sup>6</sup>, S. Shafran<sup>7</sup>, S. Pol<sup>8</sup>, F.A. Caruntu<sup>4</sup>, S. Mauss<sup>9</sup>, D. Larrey<sup>10</sup>, C. Häfner<sup>11</sup>, Y. Datsenko<sup>11</sup>, J. Stern<sup>12</sup>, R. Kubiak<sup>11</sup>, G. Steinmann<sup>11</sup><br> <em><sup>1</sup>Department of Viral Hepatitis, Johns Hopkins University, Baltimore, MD, USA, <sup>2</sup>Hôpital Saint Joseph, Marseille, <sup>3</sup>Hôpital de Brabois, Vandoeuvre Cedex, France, <sup>4</sup>'Prof. Dr. Matei Bals' Institute of Infectious Diseases 1, Bucharest, Romania, <sup>5</sup>Hôpital Beaujon, Clichy Cedex, <sup>6</sup>Hôpital Henri Mondor, Créteil, France, <sup>7</sup>University of Alberta, Edmonton, AB, Canada, <sup>8</sup>Hôpital Cochin, Paris, France, <sup>9</sup>Center for HIV and Hepatogastroenterology, Düsseldorf, Germany, <sup>10</sup>Hôpital Saint-Eloi, Montpellier Cedex, France, <sup>11</sup>Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/ Riß, Germany, <sup>12</sup>Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA. *msulkowski@jhmi.edu</em></p><br> <p align='justify'><b><b>Background and aims: </b></b> BI 201335 is a potent HCV NS3/4A protease inhibitor being studied in phase IIb trials of chronic HCV genotype-1 (GT1) infection. <br><b>Methods: </b> In a double-blind, randomized, parallel group design, HCV GT1 patients with confirmed non-response to at least 12 wks of PegIFN/RBV treatment were randomized 1:2:1 to (1) 240 mg BI 201335 once daily (QD), (2) 240 mg BI 201335 QD after a 3 day lead-in phase (LI) of PegIFN/RBV, and (3) 240 mg BI 201335 twice daily (BID) after a 3 day LI. Relapsers and patients with liver cirrhosis were excluded. In each group, treatment is for 24 wks with a background of PegIFN (180 µg/wk) and RBV (1000/1200mg/d). Pre-specified Interim analysis after 12 weeks of therapy is reported. Viral rebound is defined as an increase in plasma HCV RNA e" 1 log<sub>10</sub> on-treatment from nadir or confirmed increase e" 100 IU/ml if previously undetectable. <br><b>Results: </b> 288 patients were treated (mean age 49 +/- 9 years; mean BMI 26.4 +/- 4.4 kg/m2; mean log<sub>10</sub> HCV RNA at baseline 6.6 IU/mL). BI 201335 with PegIFN/RBV was overall well tolerated and demonstrated potent antiviral activity in all dose groups (Table). Mean ALT improved in all groups. 8% of patients prematurely discontinued treatment due to adverse events (AE). Most frequent AE were gastrointestinal disorders, mostly mild jaundice resulting from isolated unconjugated hyperbilirubinemia, (9.2%, 14.1% and 34.3% in groups 1, 2 and 3) and mostly mild to moderate rash or photosensitivity reactions (severe rash in 1.3, 0.7 and 5.7% in groups 1, 2 and 3).<br><br><br><table border=1> <tr><td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>Treatment</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>Virological Response at wk 4; < 25 IU/mL (%)</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>Virological Response at wk 12; < 25 IU/mL (%)</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>Viral Rebound at wk 12 (%)</span></td> </tr><tr><td width='25%' align='left'><span style='font-weight:normal; font-style:normal'>(1) 240 mg QD (N=76)</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>61.8</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>68.4</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>22.4</span></td> </tr><tr><td width='25%' align='left'><span style='font-weight:normal; font-style:normal'>(2) 240 mg QD / LI (N=142)</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>64.1</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>68.3</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>21.8</span></td> </tr><tr><td width='25%' align='left'><span style='font-weight:normal; font-style:normal'>(3) 240 mg BID / LI (N=70)</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>68.6</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>62.9</span></td> <td width='25%' align='center'><span style='font-weight:normal; font-style:normal'>15.7</span></td> </tr></table><i>[Virological Response and Rebound at week 12]</i><br /><br><b>Conclusions: </b> SILEN-C2 confirmed robust antiviral activity with overall good tolerability and safety of BI 201335 especially if given 240mg once daily in combination with PegIFN/RBV in patients with chronic HCV GT-1 infection who did not respond to a previous course of PegIFN/RBV therapy.<br></p> <br><a href="javascript://;" onclick="history.back()">Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>