100% Rapid Virologic Response for PSI-7977 + Ribavirin in Genotype 1 Null Responders (ELECTRON): Early Viral Decline Similar to that Observed in Genotype 1 and Genotype 2/3 Treatment-naïve Patients
Edward Gane*1, C Stedman2, J Anderson3, R Hyland3, R Hindes3, W Symonds3, and M Berrey3
1Auckland City Hosp, New Zealand; 2Christchurch Hosp, New Zealand; and 3Pharmasset, Inc, Durham, NC, US
Background: PSI-7977 is a potent uridine nucleotide analog in phase 3 development. In the phase 2 PROTON study, PSI-7977 with pegylated interferon (pegIFN)/ribavirin (RBV) achieved >90% sustained virological response in patients infected with hepatitis C virus (HCV) genotypes (GT) 1, 2, or 3. In the ELECTRON study, PSI-7977/RBV for 12 weeks without PEG achieved 100% SVR in HCV GT2/3. To evaluate the response of this pegIFN-free regimen in patients infected with HCV GT1, 2 additional cohorts were enrolled in the ELECTRON study—GT1 treatment-naïve patients and GT1 prior null responders (defined as <2 log10 reduction in HCV RNA at week 12 of a pegIFN/RBV regimen).
Methods: For 12 weeks, 20 null responders and 25 treatment-naïve, non-cirrhotic patients with HCV GT1 received 400 mg PSI-7977/RBV. Early on-treatment viral kinetics were compared to data obtained from earlier ELECTRON study cohorts of treatment-naive patients infected with HCV GT2/3.
Results: At the time of abstract submission, 9 of 10 null-responder patients have received ≥9 weeks and 13 of 25 treatment-naïve have received ≥4 weeks of treatment. Baseline patient characteristics are shown in the table. Early, on-treatment viral kinetics were similar in the 2 treatment cohorts. By week 2, mean HCV RNA decline from baseline was 5.54 log10 IU/mL in the GT1 null responders and 4.87 in the GT1 treatment-naïve patients (compared to 5.31 log in GT2/3 treatment-naïve patients); 78% of GT1 null responders and 71% GT1 treatment-naïve patients were <LOD (limit of detection 15 IU/mL) at 2 weeks (compared to 80% of treatment-naïve GT2/3 patients). All patients in both cohorts were <LOD at week 4 (i.e., 100% RVR) or last available time point. To date, no patient in ELECTRON has experienced virologic breakthrough on PSI-7977/RBV. PSI-7977/RBV was generally well tolerated, with no treatment-related SAE, discontinuations, or Grade 3/4 laboratory abnormalities.
Conclusions: This interferon-free, all-oral regimen of PSI-7977/RBV for 12 weeks was well tolerated and achieved a similar on-treatment viral suppression in HCV GT1 and GT2/3, which was independent of the usual predictors of response to pegIFN/RBV, including viral genotype, IL28B genotype and prior null-response to pegIFN/RBV.