EASL 2012: High SVR Rate in Treatment-Naïve HCV Genotype 1a and 1b Patients Treated for 12 Weeks with an Interferon-Free All-Oral Quad Regimen: Interim Results

Abstract

Title: High Sustained Virologic Response Rate in Treatment-Naïve HCV Genotype 1a and 1b Patients Treated for 12 Weeks with an Interferon-Free All-Oral Quad Regimen: Interim Results

Speaker: Mark Sulkowski

Author: M. Sulkowski¹*, M. Rodriguez-Torres², E. Lawitz³, M. Shiffman⁴, S. Pol⁵, R. Herring⁶, J. McHutchison⁷, P. Pang⁷, D. Brainard⁷, D. Wyles⁸, F. Habersetzer⁹

Affiliation: ¹Johns Hopkins University School of Medicine, Lutherville, MD, USA, ²Fundacion de Investigacion de Diego, Santurce, Puerto Rico, ³Alamo Medical Research, San Antonio, TX, ⁴Liver Institute of Virginia, Richmond, VA, USA, ⁵Hôpital Necker, Paris, France, ⁶Nashville Gastrointestinal Specialists, Inc., Nashville, TN, ⁷Gilead Sciences, Inc., Foster City, ⁸University of California, San Diego, La Jolla, CA, USA, ⁹Hôpitaux Universitaires de Strasbourg, Strasbourg, France. *msulkowski@jhmi.edu

Background and aims: The efficacy and safety of an all-oral regimen of the NS5a inhibitor GS-5885, non-nucleoside NS5b inhibitor tegobuvir, NS3 protease inhibitor GS-9451, and ribavirin for 12 or 24 weeks were assessed in chronic HCV genotype (GT) 1-infected patients. We report interim results in patients who received a 12-week treatment regimen.

Methods: 141 treatment-naïve patients were randomized 1:2 to receive GS-5885 30mg/day (Arm 1; n=47) or GS-5885 90mg/day (Arm 2; n=94); patients in both arms received tegobuvir 30mg BID + GS-9451 200mg QD + ribavirin 1000-1200mg/day. Patients not achieving HCV RNA < 25 IU/mL at Week 2 (vRVR; Roche Cobas Taqman v2 with LLOQ=25 IU/mL) were switched to peginterferon-containing rescue therapy. Arm 2 patients who achieved vRVR and remained undetectable were re-randomized (1:1) at Week 12 to stop therapy immediately or continue for an additional 12 weeks (total duration, 24 weeks).

Results: 94 patients randomized to Arm 2 received treatment: 59% male, 12% black, 60% non-CC allele, 72% GT1a, 87% HCV RNA >600,000 IU/mL. 74 achieved vRVR and 64 were eligible for re-randomization at Week 12. 27/33 patients who stopped therapy at Week 12 have reached post-treatment Week 4. Of these, 26 (96%) achieved SVR4 (18/19 [95%] of the GT1a patients and all 8 GT1b patients). Viral breakthrough occurred only in GT1a patients (8/55). Two patients terminated early: 1 due to alcohol abuse and 1 withdrew consent. IL28B status did not appear to correlate with SVR4 or breakthrough. The most frequently reported AEs were headache (21%), fatigue (16%), diarrhea (14%), nausea (13%), and rash (11%). No WBC or platelet reductions were observed. Mean hemoglobin reduction was -2.3 g/dL. No patients were discontinued from all-oral therapy due to a drug-related adverse event.

Conclusions: High SVR rates were observed with this well-tolerated, 12-week, interferon-free, all-oral quad regimen in HCV GT1a and 1b patients who achieved vRVR and remained undetectable during 12 weeks of therapy. Viral breakthrough and relapse were limited to GT1a-infected patients.

[Study Flow Chart]

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