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 2011 - 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 15: Late-Breakers<br><b>Presentation Date:</b> 31 March - 2, April, 2011</P><h2 align='left'><B><B>ONCE DAILY DUAL-NUCLEOTIDE COMBINATION OF PSI-938 AND PSI-7977 PROVIDES 94% HCV RNA < LOD AT DAY 14: FIRST PURINE/PYRIMIDINE CLINICAL COMBINATION DATA (THE NUCLEAR STUDY)</B></B></h2> <p align='left'><b>E. Lawitz</b><sup>1</sup>*, M. Rodriguez-Torres<sup>2</sup>, J. Denning<sup>3</sup>, M. Cornpropst<sup>3</sup>, D. Clemons<sup>3</sup>, L. Mcnair<sup>3</sup>, M.M. Berrey<sup>3</sup>, W. Symonds<sup>3</sup><br> <em><sup>1</sup>Alamo Medical Resarch, San Antonio, TX, <sup>2</sup>Fundacion de Investigacion De Diego, San Juan, PR, <sup>3</sup>Pharmasset, Inc., Princeton, NJ, USA. *lawitz@alamomedicalresearch.com</em></p><br> <p align='justify'><b><b>Background: </b> </b>PSI-938 (purine) and PSI-7977 (pyrimidine) are nucleotide analogs in development for the treatment of HCV infection. Complementary resistance profiles, high barriers to resistance, broad genotype coverage, and independent phosphorylation pathways characterize this potentially ideal DAA combination.<br><b><b>Methods: </b></b> Treatment-naïve, non-cirrhotic patients with HCV GT1 received: 1) PSI-938 for 14 days; 2) PSI-938 days 1-7 and PSI-938+PSI-7977 days 8-14; 3) PSI-7977 days 1-7 and PSI-938+PSI-7977 days 8-14; or 4) PSI-938+PSI-7977 for 14 days. 10 patients per cohort (2 placebo) received PSI-938 300mg QD and/or PSI-7977 400mg QD. Safety, pharmacokinetics, HCV RNA, and viral resistance were assessed.<br><b><b>Results: </b> </b>30 patients were enrolled in cohorts 1-3 with baseline HCV RNA values of 7.0, 6.2 and 6.3 log<sub>10</sub> IU/mL, respectively. Monotherapy (14 days) and 7+7 day combinations were generally safe and well tolerated with no SAEs and no discontinuations. Steady-state pharmacokinetics from monotherapy (day 7) and the combination (day 14) confirmed the absence of clinically-relevant PK interactions between PSI-7977 and PSI-938. Monotherapy PSI-938, monotherapy PSI-7977, or combination PSI-938+PSI-7977 provided profound and consistent reductions in HCV RNA with HCV RNA < LOD (15 IU/mL) as early as day 3 of the monotherapy phase. <br><br><img hspace=5 vspace=5 src=pictures/p_343_00369.jpg ><br><i>[The Nuclear Study HCV RNA]</i><br>PSI-938 300mg QD for 14 days yielded 50% (4/8) < LOD and 63% (5/8) < LOQ (43 IU/mL). The addition of the second nucleotide on day 8 provided incremental antiviral effect, with 94% (15/16) combination subjects' HCV RNA < LOD and 100% < LOQ by day 14. Median reductions from baseline in HCV RNA ranged from 5.0 to 5.2 log<sub>10</sub> IU/mL across cohorts 1-3. The final cohort of PSI-938+PSI-7977 for a full 14 days (cohort 4) has completed enrollment. <br><b>Conclusions</b>: PSI-938+PSI-7977 is the first purine+pyrimidine combination explored in HCV. Monotherapy with either nucleotide analog provided profound antiviral responses rivaling the best antiviral responses reported by combinations employing 2 or more DAAs. This 14-day proof-of-concept study demonstrates excellent safety/tolerability, lack of antagonism (PK or antiviral), and no virologic breakthrough. A Phase 2 study enrolling all HCV genotypes will explore different durations of this promising purine+pyrimidine combination.</p> <img src='pictures/p_343_00369.jpg'> <br><a href='Session-LBP01.htm'>Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>