Efficacy of the Protease Inhibitor BI 201335, Polymerase Inhibitor BI 207127, and Ribavirin in Patients With Chronic HCV Infection

Virus de l’hépatite C

“…Ils sont indispensables, notamment chez les patients ayant une fibrose extensive, une fibrose intermédiaire ou une cirrhose, mais des comorbidités hépatiques (surconsommation d'alcool, surpoids) favorisent une progression rapide de la fibrose [4,22]. De nombreux autres antiviraux ont été développés, tels que les inhibiteurs de la polymérase NS5B de type nucléotidiques [23,24] ou non [24], les inhibiteurs du complexe de réplication NS5A [25] et les inhibiteurs de protéases de deuxième génération [26,27]. Ces nouveaux antiviraux ont été, dans un premier temps, associés à l'interféron pégylé et la ribavirine, permettant d'obtenir une guérison des patients dans 75 à 95 % des cas (Figure 4).…”

All-oral combination of ledipasvir, vedroprevir, tegobuvir, and ribavirin in treatment-naïve patients with genotype 1 HCV infection

“…5,6 The first trial to confirm achievement of SVR with an IFN-free regimen was a small study in which 11 previous null responders receiving the NS5A inhibitor, daclatasvir, and the NS3 protease inhibitor, asunaprevir, achieved an SVR rate of 36%. 5 Six patients had virologic breakthrough during therapy with the combination; all were infected with HCV genotype 1a, and resistance mutations to both targeted proteins were found in all cases.…”

“…In a phase I trial employing a more potent three-drug regimen containing two DAAs (BI 201335, an NS3 protease inhibitor, and BI 207127, an NS5B polymerase inhibitor) and RBV, rapid and high rates of on-treatment virologic response (82%-100%) in both HCV genotype 1a-and genotype 1b-infected patients were achieved. 6 Likewise, in a small phase IIa exploratory study, ABT-450 (an HCV NS3 protease inhibitor) boosted with low-dose ritonavir, in addition to ABT-333 (a non-nucleoside NS5B polymerase inhibitor) and RBV, led to SVR12 rates of 93% to 95% in previously untreated patients with HCV genotype 1 infection. 13 Thus, as potency of the IFN-free regimen increased, so did virologic response.…”

“…From the 1 University of California, San Diego, La Jolla, CA; 2 Fundacion de Investigacion de Diego, Santurce, Puerto Rico; 3 Texas Liver Institute, San Antonio, TX; 4 Liver Institute of Virginia, Richmond, VA; 5 Hôpital Cochin, Paris, France; 6 Quality Medical Research, PLLC, Nashville, TN; 7 Gilead Sciences, Inc., Foster City, CA; 8 Inserm 1110, Universite de Strasbourg, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; and 9 Johns Hopkins University School of Medicine, Baltimore, MD.…”

“…Studies investigating DAA combinations have shown that SVR can be achieved with shorter treatment durations and in the absence of IFN. 5,6 In this phase II trial, we assessed the safety and efficacy of a combination regimen consisting of ledipasvir (LDV), an inhibitor of the nonstructural (NS)5A protein, vedroprevir (VDV; previously known as GS-9451), a reversible noncovalent inhibitor of the HCV NS3/4A serine protease, tegobuvir (TGV), a non-nucleoside inhibitor of the HCV NS5B polymerase, and RBV. Individually, these agents have demonstrated antiviral activity against genotype 1 HCV.…”