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 - Poster 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-congress/PublishingImages/top_ei.jpg" width="760" height="129" /></td> </tr> <tr> <td class="content"><h1>Poster Presentations</h1> <P><b>Session Title:</b> Category 13. LATE-BREAKERS<br><b>Presentation Date:</b> Apr 15, 2010</P><h2 align='left'><B>LONG-TERM OUTCOMES FOLLOWING COMBINATION TREATMENT WITH BOCEPREVIR PLUS PEG-INTRON/RIBAVIRIN (P/R) IN PATIENTS WITH CHRONIC HEPATITIS C, GENOTYPE 1 (CHC-G1)</B></h2> <p align='left'><b>J.M. Vierling</b><sup>1</sup>*, R. Ralston<sup>2</sup>, E.J. Lawitz<sup>3</sup>, J. McCone<sup>4</sup>, S. Gordon<sup>5</sup>, D. Pound<sup>6</sup>, M. Davis<sup>7</sup>, J. Galati<sup>8</sup>, I. Jacobson<sup>9</sup>, L. Rossaro<sup>10</sup>, F.H. Anderson<sup>11</sup>, J. King<sup>12</sup>, W. Cassidy<sup>13</sup>, M. Bourliere<sup>14</sup>, R. Esteban-Mur<sup>15</sup>, N. Ravendhran<sup>16</sup>, G. Galler<sup>17</sup>, P. Mendez<sup>2</sup>, C.A. Brass<sup>2</sup>, J.K. Albrecht<sup>2</sup><br> <em><sup>1</sup>Advanced Liver Therapies/St. Luke's Episcopal Hospital, Houston, TX, <sup>2</sup>Merck Research Laboratories, Kenilworth, NJ, <sup>3</sup>Alamo Medical Research, San Antonio, TX, <sup>4</sup>Mount Vernon Endoscopy Center, Alexandria, VA, <sup>5</sup>Henry Ford Hospitals, Detroit, MI, <sup>6</sup>Indianapolis Gastroenterology Research Foundation, Indianapolis, IN, <sup>7</sup>South Florida Center of Gastroenterology, Wellington, FL, <sup>8</sup>Liver Specialists of Texas, Houston, TX, <sup>9</sup>Weill Medical College of Cornell University, New York, NY, <sup>10</sup>Davis Medical Center, University of California, Sacramento, CA, USA, <sup>11</sup>The Liver and Intestinal Research Centre, Vancouver, BC, Canada, <sup>12</sup>LSU Medical Center; Louisiana State University, Shreveport, <sup>13</sup>Louisiana State University, Baton Rouge, LA, USA, <sup>14</sup>Hospital Saint Joseph, Marseille Cedex, France, <sup>15</sup>Hospital Vall d'Hebron, Barcelona, Spain, <sup>16</sup>Digestive Disease Associates, Baltimore, MD, <sup>17</sup>Kelsey Research Foundation, Houston, TX, USA. *vierling@bcm.tmc.edu</em></p><br> <p align='justify'><b>Background</b><b>:</b> Combination treatment of CHC-G1 with boceprevir, an inhibitor of the HCV NS3 serine protease, leads to high rates of sustained virologic response (SVR). The durability of SVR and the natural history of resistance mutations in patients not responding to therapy are unknown. To characterize long-term outcomes, patients who participated in boceprevir trials are being monitored for 3 years post-therapy.<br><b><b>Methods: </b> </b>We evaluated samples from 604 patients (treatment-naïve or P/R failures) who received boceprevir plus Peg-Intron ± ribavirin in 2 phase II trials. HCV-RNA was detected using Roche Taqman (LLD= 29 IU/mL). Resistance mutations were detected by population sequencing of the NS3 protease region (codons 1-181) by Virco BBVA (Belgium) and/or by sponsor. Kaplan-Meier analysis was used to compare the loss of detectable resistance mutations in the NS3 1-181 sequence. <br><b>Results</b><b>: </b>No late relapse was confirmed in the 290 subjects who previously had SVR. A total of 25 serious adverse events (SAEs) occurred, and all were similar to those previously described in long-term follow-up. An additional 172 subjects who did not achieve SVR were followed for e"2 years, from the naïve trial (38/373; 16%) and from the treatment failure trial (134/226; 59%) in which no patient received the current treatment regimen. We identified 18 boceprevir resistant mutations in the following proportions: R155K, 64%; T54S, 54%; V36M, 54%; T54A, 22%; others < 9% each. The rate of return to wild type NS3 1-181 sequence was higher for patients with V36M compared to those with T54S or R155K . <br><br><img hspace=5 vspace=5 src=pictures/p_248_00234.jpg ><br><i>[Loss of Detectable Resistance Mutations]</i><br><br><b>Conclusion</b><b>: </b>SVR following boceprevir combination therapy was durable. There were no latent SAEs or laboratory abnormalities related to prior treatment. Specific resistance mutations to boceprevir declined at different rates, V36M declined fastest; T54S and R155K declined at similar rates. Variation in the rate of mutational decline likely reflects the relative fitness of the mutants.</p> <img src='pictures/p_248_00234.jpg'> <br><a href='Session-PLB-13.htm'>Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>