Thématique :
- Foie
Originalité :
Solidité :
Doit faire évoluer notre pratique :
Pas encore
Nom du veilleur :
Professeur Jean-Marie PERON
Coup de coeur :
  2016 Jul 30. pii: S0016-5085(16)34835-1  
  doi: 10.1053/j.gastro.2016.07.039  
  Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients with Genotype 1 Hepatitis C Virus Infection in an Open-label, Phase 2 Trial.  
  Lawitz E, Reau N, Hinestrosa F, Rabinovitz M, Schiff E, Sheikh A, Younes Z, Herring R Jr, Reddy KR, Tran T, Bennett M, Nahass R, Yang JC, Lu S, Dvory-Sobol H, Stamm LM, Brainard DM, McHutchison JG, Pearlman B, Shiffman M, Hawkins T, Curry M, Jacobson I  


The best regimen to retreat patients who do not respond to direct-acting antivirals (DAAs) and the feasibility of further shortening regimens is unclear. We assessed the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus (HCV) genotype 1 infection.


We performed an open-label trial at 32 sites in the United States and 2 sites in New Zealand of 197 patients with genotype 1 HCV infection, with or without compensated cirrhosis, who were treatment-naïve or previously treated with a DAA. Between March 2 and September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a fixed-dose combination) plus GS-9857 (100 mg) once daily for 6-12 weeks, plus ribavirin for one treatment group consisting of treatment-naïve patients with cirrhosis. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12).


Among treatment-naïve patients without cirrhosis, 71% (24/34; 95% CI, 53-85) achieved SVR12 after 6 weeks of treatment and 100% (36/36; 95% CI, 90%-100%) after 8 weeks of treatment. Among treatment-naïve patients with cirrhosis, 94% (31/33; 95% CI, 80-99) achieved SVR12 after 8 weeks of treatment and 81% (25/31; 95% CI, 63-93) after 8 weeks of treatment with ribavirin. Among DAA-experienced patients treated for 12 weeks, 100% without cirrhosis (31/31; 95% CI, 89-100) and 100% with cirrhosis (32/32; 95% CI, 89-100) achieved SVR12. The most common adverse events were headache, diarrhea, fatigue, and nausea. One patient (<1%) discontinued treatment due to adverse events.


In a phase 2 open-label trial, we found 8 weeks treatment with sofosbuvir-velpatasvir plus GS-9857 to be safe and effective in treatment-naïve patients; 12 weeks was safe and effective in patients previously treated with DAAs. The combination was safe and effective in patients with or without compensated cirrhosis. no: NCT02378935.

Question posée
Phase 2, traitement court par la trithérapie GILEAD (sofosbuvir velpatasvir GS 9857) des génotypes 1 au stade de cirrhose ou non ?
Question posée
Bonne tolérance. Bonne efficacité d’un traitement de 8 semaines pour les patients naïfs et 12 semaines pour les patients antérieurement traités.