Alisporivir plus ribavirin, interferon free or in combination with pegylated interferon, for hepatitis C virus genotype 2 or 3 infection. Issue 4 (10th August 2015)

• Record Type: Journal Article
• Authors: Pawlotsky, Jean‐Michel; Flisiak, Robert; Sarin, Shiv K.; Rasenack, Jens; Piratvisuth, Teerha; Chuang, Wan‐Long; Peng, Cheng‐Yuan; Foster, Graham R.; Shah, Samir; Wedemeyer, Heiner; Hézode, Christophe; Zhang, Wei; Wong, Kelly A.; Li, Bin; Avila, Claudio; Naoumov, Nikolai V.; on behalf of the VITAL‐1 study team
• Is Part Of: Hepatology. Volume 62:Issue 4(2015:Oct.)
• Page Start: 1013
• Page End: 1023
• Publication Date: 2015-08-10
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.27960
• Languages: English
• ISSNs: 0270-9139

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Alisporivir is a cyclophilin inhibitor with pan‐genotypic anti–hepatitis C virus (HCV) activity and a high barrier to viral resistance. The VITAL‐1 study assessed alisporivir as interferon (IFN)‐free therapy in treatment‐naïve patients infected with HCV genotype 2 or 3. Three hundred forty patients without cirrhosis were randomized to: arm 1, alisporivir (ALV) 1, 000 mg once‐daily (QD); arm 2, ALV 600 mg QD and ribavirin (RBV); arm 3, ALV 800 mg QD and RBV; arm 4, ALV 600 mg QD and pegylated IFN (Peg‐IFN); or arm 5, Peg‐IFN and RBV. Patients receiving IFN‐free ALV regimens who achieved rapid virological response (RVR) continued the same treatment throughout, whereas those with detectable HCV RNA at week 4 received ALV, RBV, and Peg‐IFN from weeks 6 to 24. Overall, 300 patients received ALV‐based regimens. In arm 1 to arm 4, the intent‐to‐treat rates of sustained virological response (SVR) 24 weeks after treatment (SVR24) were from 80% to 85%, compared with 58% (n = 23 of 40) with Peg‐IFN/RBV. Per‐protocol analysis showed higher SVR24 rates in patients who received ALV/RBV, IFN‐free after RVR (92%; n = 56 of 61) than with ALV alone after RVR (72%; n = 13 of 18) or with Peg‐IFN/RBV (70%; n = 23 of 33). Both RVRs and SVRs to ALV IFN‐free regimens were numerically higher in genotype 3– than in genotype 2–infected patients. Viral breakthrough was infrequent (3%; n = 7 of 258). IFN‐free ALV treatment showed markedly better safety/tolerability than IFN‐containing regimens. <italic>Conclusions</italic>: ALV plus RBV represents an effective IFN‐free option for a proportion of patients with HCV genotype 2 or 3 infections, with high SVR rates for patients with early viral clearance. Further investigations of ALV in IFN‐free combination regimens with direct‐acting antiviral drugs deserve exploration in future trials. (H<sc>epatology</sc> 2015;62:1013‐1023)</p> </abstract>