Hepatology. 2014 Feb 5. doi: 10.1002/hep.27053. [Epub ahead of print]
Wyles DL, Rodriguez-Torres M, Lawitz E, Shiffman ML, Pol S, Herring RW, Massetto B, Kanwar B, Trenkle JD, Pang PS, Zhu Y, Mo H, Brainard DM,Subramanian GM, McHutchison JG, Habersetzer F, Sulkowski MS.
This phase 2 trial assessed the efficacy and safety of a combination regimen of the NS5A inhibitor ledipasvir (LDV), NS3 protease inhibitor vedroprevir (VDV), nonnucleoside NS5B inhibitor tegobuvir (TGV), and ribavirin (RBV) in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 without cirrhosis. Patients were randomized 1:2 to LDV 30 mg once daily (QD) (Arm 1; n = 46) or LDV 90 mg QD (Arm 2; n = 94); patients in both arms also received VDV 200 mg QD, TGV 30 mg twice daily, and RBV 1000-1200 mg/day. Patients in Arm 2 with vRVR, defined as HCV RNA <LLOQ from treatment weeks 2-10, were randomized 1:1 to stop treatment at 12 weeks or continue for 24 weeks. Sustained virologic response 12 weeks after treatment (SVR12) was higher in patients receiving 90 mg LDV for 24 weeks (63%) compared to LDV 90 mg for 12 weeks (54%) and LDV 30 mg for 24 weeks (48%). In patients with vRVR in Arm 2, SVR12 was achieved by 68% and 81% of patients treated for 12 and 24 weeks, respectively. Virologic breakthrough was more common in patients with HCV genotype 1a and was associated with resistance-associated variants for all three direct-acting antiviral agents (DAAs); however, in all but 1 patient who relapsed, RAVs directed against only one or two of the DAAs were detected. The most common adverse events were fatigue, headache, nausea, rash, and diarrhea. Conclusion: In patients with HCV genotype 1, an interferon-free regimen containing LDV/VDV/TGV/RBV was well tolerated and led to SVR12 in up to 63% of patients. LDV 90 mg is currently being investigated in combination with the nucleotide polymerase inhibitor sofosbuvir. (Hepatology 2014;).
Copyright © 2014 American Association for the Study of Liver Diseases.
KEYWORDS: NS3 protease inhibitor, NS5A inhibitor, antiviral therapy, hepatitis C, nonnucleoside NS5B polymerase inhibitor
PMID: 24501005 [PubMed - as supplied by publisher]