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 2009 - 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-congress/PublishingImages/top760.jpg" width="760" height="181" /></td> </tr> <tr> <td class="content"><h1>Oral Presentations</h1> <P><b>Session Title:</b> OPENING AND GENERAL SESSION 1<br><b>Presentation Date:</b> Apr 23, 2009</P><h2 align='left'><b>HCV SPRINT-1 FINAL RESULTS : SVR 24 FROM A PHASE 2 STUDY OF BOCEPREVIR PLUS PEGINTRON<sup>TM</sup> (PEGINTERFERON ALFA-2B)/RIBAVIRIN IN TREATMENT-NAÏVE SUBJECTS WITH GENOTYPE-1 CHRONIC HEPATITIS</b> <b>C</b></h2> <p align='left'><b>P. Kwo</b><sup>1</sup>, E. Lawitz<sup>2</sup>, J. McCone<sup>3</sup>, E. Schiff<sup>4</sup>, J. Vierling<sup>5</sup>, D. Pound<sup>6</sup>, M. Davis<sup>7</sup>, J. Galati<sup>8</sup>, S. Gordon<sup>9</sup>, N. Ravendhran<sup>10</sup>, L. Rossaro<sup>11</sup>, F. Anderson<sup>12</sup>, I. Jacobson<sup>13</sup>, R. Rubin<sup>14</sup>, K. Koury<sup>15</sup>, C. Brass<sup>15</sup>, E. Chaudhri<sup>15</sup>, J. Albrecht<sup>15</sup><br> <em><sup>1</sup>Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, <sup>2</sup>Alamo Medical Research, San Antonio, TX, <sup>3</sup>Mount Vernon Endoscopy Center, Alexandria, VA, <sup>4</sup>Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL, <sup>5</sup>Professor of Medicine and Surgery, Baylor College of Medicine, Houston, TX, <sup>6</sup>Indianapolis Gastroenterology Research Foundation, Indianapolis, IN, <sup>7</sup>Digestive Care/South Florida Center of Gastroenterology, Wellington, FL, <sup>8</sup>Liver Specialists of Texas, Houston, TX, <sup>9</sup>Department of Hepatology, Henry Ford Health Systems, Detroit, MI, <sup>10</sup>Digestive Disease Associates, Baltimore, MD, <sup>11</sup>Internal Medicine, University of California-Davis Medical Center, Sacramento, CA, USA, <sup>12</sup>The Liver & Intestinal Research Center, Vancouver, BC, Canada, <sup>13</sup>Weill Cornell Medical College, New York, NY, <sup>14</sup>Digestive Healthcare of Georgia, Atlanta, GA, <sup>15</sup>Schering-Plough Research Institute, Kenilworth, NJ, USA</em></p><br> <p align='justify'><b><b>Background: </b> </b>HCV SPRINT-1 assessed the safety and efficacy of boceprevir, an oral inhibitor of HCV-NS3 protease, plus PegIntron (P) (1.5 µg/kg/QW) and ribavirin (R) (400-1400 mg/day).<br><b><b>Methods: </b> </b>P/R(800-1400 mg/day) for 48 weeks compared to five boceprevir(800 mg TID) regimens: 4 weeks of P/R lead-in followed by P/R(800-1400 mg/day)/boceprevir for 24 or 44 weeks; P/R(800-1400 mg/day)/boceprevir for 28 or 48 weeks; and P/low-dose R(400-1000 mg/day)/boceprevir for 48 weeks. The primary endpoint was sustained virologic response (SVR) at 24 weeks post-treatment (Roche TaqMan LLD=15 IU/mL). <br><b><b>Results: </b></b> Of 595 patients treated in US (77%), Canada and Europe, 60% were male, 16% Black, 7% cirrhotic, 56% genotype 1a and 89% had high viral load (>600,000 IU/mL). SVR was significantly increased in the 28 and 48 week boceprevir arms compared to P/R Control. RVR<sup> </sup> and EVR<sup> </sup> were highly predictive of SVR with boceprevir combinations. Rash-related AEs were similar for boceprevir regimens and P/R Control.<br><br><br><table border=1> <tr><td width='14%' align='center'> </td> <td width='14%' align='center' colspan='3'><span style='font-weight:normal; font-style:normal'>Sustained Viriologic Response %<br>(n/N)*</span></td> <td width='14%' align='center'> </td> <td width='14%' align='center'> </td> <td width='14%' align='center'> </td> </tr><tr><td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>Treatment Arm</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>All Patients</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>Patients with RVR<sup> </span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>Patients with EVR<sup> </span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>Relapse Rate % (n/N)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>Discontunuation due to AE <br>% (n/N)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>Viral** Breakthrough % (n/N)</span></td> </tr><tr><td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>P/R Control 48 Weeks</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>38%<br> (39/104)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>100%<br> (8/8)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>86%<br> (32/37)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>24%<br> (12/50)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>8%<br> (8/104)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>0</span></td> </tr><tr><td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>P/R/B<br>28 Weeks</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>55%+ <br> (59/107)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>74%<br> (32/43)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>69%<br> (59/85)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>30%<br> (24/81)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>11%<br> (12/107)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>7%<br> (7/107)</span></td> </tr><tr><td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>P/R Lead-In ’! P/R/B<br>28 Weeks</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>56%++<br> (58/103)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>82%<br> (54/66)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>68%<br> (58/85)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>24%<br> (18/76)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>15%<br> (15/103)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>4%<br> (4/103)</span></td> </tr><tr><td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>P/R/B <br>48 Weeks</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>67%+++<br> (69/103)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>84%<br> (32/38)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>84%<br> (68/81)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>7%<br> (5/73)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>19%<br> (20/103)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>12%<br> (12/103)</span></td> </tr><tr><td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>P/R Lead-In ’! P/R/B <br>48 Weeks</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>75%+++<br> (77/103)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>94%<br> (62/66)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>91%<br> (77/85)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>3%<br> (2/79)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>9%<br> (9/103)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>5%<br> (5/103)</span></td> </tr><tr><td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>P/R/B <br>48 Weeks***</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>50%<br> (8/16)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>86%<br> (6/7)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>73%<br> (8/11)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>11%<br> (1/9)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>25%<br> (4/16)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>25%<br> (4/16)</span></td> </tr><tr><td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>P/Low <br>Dose R/B <br>48 Weeks***</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>36%<br> (21/59)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>75%<br> (12/16)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>60%<br> 21/35</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>23%<br> (6/26)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>12%<br> (7/59)</span></td> <td width='14%' align='center'><span style='font-weight:normal; font-style:normal'>27%<br> (16/59)</span></td> </tr></table><i>[Table 1]</i><br /><br> Undetectable HCV-RNA d"4 weeks boceprevir <br> Undetectable HCV-RNA d"12 weeks boceprevir <br>*Per protocol, if e" 24 week post-treatment not available, 12 week post-treatment assessment utilized <br>**Persistent e" 2 log<sub>10</sub> increase from nadir and e"50,000 IU/mL <br>***In Part 2, 75 patients randomized 1:4 to full vs low dose ribavirin plus P/B for 48 weeks <br>+p=0.0082, ++p=0.0048, +++p< 0.0001 adjusted for baseline stratification <br><b>Conclusions</b>: Both 28 and 48 week boceprevir regimens significantly increased SVR with very low relapse rates in 48 week regimens. However, low dose ribavirin with PegIntron and boceprevir was associated with increased viral breakthrough, relapse and lower efficacy. In contrast, P/R lead-in prior to boceprevir substantially increased SVR and reduced viral breakthrough.</p> <br><a href="javascript://;" onclick="history.back()">Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>