Once Daily Sofosbuvir/Ledipasvir Fixed Dose Combination with or without Ribavirin: the ELECTRON trial
Edward J. Gane1, Catherine A. Stedman2, Robert H. Hyland3, Xiao Ding3, Evguenio S. Svarovskoia3, Phil S. Pang3, William T. Symonds3
1Auckland Clinical Studies, Auckland, New Zealand; 2Christchurch Clinical Studies Trust, Christchurch, New Zealand; 3Gilead Science, Inc, Foster City, CA
Background: In previous Phase 2 studies, the addition of an NS5A inhibitor (either l edipasvir (LDV) or daclatasvir) to the combination of the HCV nucleotide analog sofosbuvir (SOF) plus ribavirin (RBV) for 12 weeks resulted in high rates of sustained viral response (SVR) in non-cirrhotic patients infected with HCV genotype 1 (GT-1). In the ELECTRON Phase 2 study, we evaluated the safety and efficacy of a fixed-dose combination (FDC) tablet of SOF plus LDV in additional patient populations, including those with cirrhosis and with non-GT-1 infection. We also evaluated the need for RBV and for 12 weeks' duration. Methods: We enrolled 4 arms: prior null-responder HCV GT-1 patients with compensated cirrhosis were randomized to receive open-label SOF/LDV FDC with or without RBV for 12 weeks; treatment-naīve HCV GT-1 patients without cirrhosis received SOF/LDV FDC plus RBV for 6 weeks; and treatment-naϊve HCV non-GT-1 patients without cirrhosis were assigned to receive SOF/LDV FDC plus RBV for 12 weeks. Results: 54 patients were enrolled. Of the GT-1 prior null-responder group, 79% were genotype 1a, and 32% were IL28B CC. Of the treatment-naϊve GT-1 group, 84% were genotype 1a, and 20% were IL28B CC. Of the non-GT-1 group 20% were GT-2, and 80% GT-3.Efficacy results are tabulated. SOF/LDV FDC with or without RBV was generally well tolerated; There were no SAEs or treatment discontinuations. Adverse events were generally mild, and Grade 3/4 laboratory abnormalities were infrequent and consistent with the safety profile of RBV. No toxicity attributable to SOF/LDV FDC was identified. Conclusions: SOF/LDV FDC elicited rapid decline in HCV RNA in all patient populations with no viral breakthrough observed. In treatment-naīve GT-1 patients without cirrhosis, reduction in duration from 12 to 6 weeks increased the rate of relapse. In the prior null responder GT-1 patients with cirrhosis, the addition of RBV to SOF/LDV FDC decreased the rate of relapse, suggesting that either RBV or a third DAA may be useful in this difficult-to-treat patient population. Promising SVR rates achieved in genotype 2 or 3 patients support further evaluation of SOF/LDV FDC in patients with HCV GT-2 or GT-3.
|Randomized GT 1 Prior Null Responders (Cirrhotics)||GT 1 Treatment Nave (Non-Cirrhotics)||GT 2/3 Treatment Nave (Non-Cirrhotics)|
|SOF/LDV FDC x 12 weeks (n=10)||SOF/LDV FDC+RBV x 12 weeks (n=9)||SOF/LDV FDC+RBV x 6 weeks (n=25)||SOF/LDV FDC x 12 weeks (n=10)|
Edward J. Gane - Advisory Committees or Review Panels: Roche, AbbVie, Novartis, Tibotec, Gilead Sciences, Janssen Cilag, Vertex, Achillion; Speaking and Teaching: Novartis, Gilead Sciences, Roche
Catherine A. Stedman - Advisory Committees or Review Panels: Jansen; Speaking and Teaching: Gilead
Robert H. Hyland - Employment: Gilead Sciences, Inc Xiao Ding - Employment: Gilead Sciences
Evguenia S. Svarovskaia - Employment: Gilead Sciences Inc.; Stock Shareholder: Gilead Sciences Inc.
Phil S. Pang - Employment: Gilead Sciences William T. Symonds - Employment: Gilead