Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment‐naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II). Issue 7 (4th August 2015)

• Record Type: Journal Article
• Authors: Zeuzem, S.; Flisiak, R.; Vierling, J. M.; Mazur, W.; Mazzella, G.; Thongsawat, S.; Abdurakhmanov, D.; Van Kính, N.; Calistru, P.; Heo, J.; Stanciu, C.; Gould, M.; Makara, M.; Hsu, S.‐J.; Buggisch, P.; Samuel, D.; Mutimer, D.; Nault, B.; Merz, M.; Bao, W.; Griffel, L. H.; Brass, C.; Naoumov, N. V.; the ESSENTIAL II Study Group; Tanno, Hugo; Bessone, Fernando; Terg, Ruben; Frider, Bernardo; Bertuzzi, Romina; Desmond, Paul; Zekry, Amany; Weltman, Martin; George, Jacob; Crawford, Darrell; Matthews, Gail; Moreno, Christophe; Van Vlierberghe, Hans; Reynaert, Hendrik; Gould, Michael; Lee, Samuel; Ramji, Alnoor; Tam, Edward; Marotta, Paul; Yoshida, Eric; Wong, Florence; Feld, Jordan; Samuel, Didier; Marcellin, Patrick; Alric, Laurent; Zarski, Jean‐Pierre; Zoulim, Fabien; Buggisch, Peter; Hinrichsen, Holger; Goeser, Tobias; Zeuzem, Stefan; Galle, Peter; Berg, Thomas; Schott, Eckart; Rasenack, Jens; Gerken, Guido; Wedemeyer, Hans; Tsang, Owen; Yuen, Man‐Fung; Chan, Henry; Hui, Aric Josun; Makara, Mihaly; Tornai, Istvan; Gervain, Judit; Szalay, Ferenc; Varga, Marta; Horvath, Gabor; Hunyady, Bela; Vincze, Aron; Mazzella, Giuseppe; Gaeta, Giovanni Battista; Alberti, Alfredo; Colombo, Massimo; Andreone, Pietro; Rizzetto, Mario; Angelico, Mario; Craxi, Antonio; Picciotto, Antonino; Sacchi, Paolo; Vinci, Maria; Invernizzi, Pietro; Bruno, Savino; Heo, Jeong; Lee, Younjae; Cho, Mong; Han, Sangyoung; Lee, Jinwoo; Ahn, Sanghoon; Lim, Youngsuk; Hwang, Seonggyu; Sanchez, Juan; Muñoz, Linda; Maldonado, Hector; Mazur, Wlodzimierz; Flisiak, Robert; Jablkowski, Maciej; Kryczka, Wieslaw; Halota, Waldemar; Calistru, Petre; Prelipcean, Cristina; Musa, Manuela; Stanciu, Carol; Manuc, Mircea; Tanasescu, Coman; Dumitrascu, Dan; Abdurakhmanov, Djamal; Chulanov, Vladimir; Nikitin, Igor; Zhdanov, Konstantin; Esaulenko, Elena; Maevskaya, Marina; Znoyko, Olga; Lamoglia, Ricard Sola; Ferret, Maria Buti; Garcia‐Samaniego, Javier; Gomez, Manuel Romero; Diago, Moises; Calleja, Jose Luis; Hsu, Shih‐Jer; Chuang, Wan‐Long; Hu, Tsung‐Hui; Peng, Cheng‐Yuan; Chen, Chi‐Yi; Kao, Jia‐Horng; Thongsawat, Satawat; Sukeepaisarnjaroen, Wattana; Piratvisuth, Teerha; Tanwandee, Tawesak; Komolmit, Piyawat; Agarwal, Kosh; Mutimer, David; Brown, Ashley; Foster, Graham; McPherson, Stuart; Ryder, Stephen; Poulos, John; Rustgi, Vinod; Lyche, Kip; Omarro, Steven; Vierling, John; Ghalib, Reem; Karnam, Umaprasanna; Peine, Craig; Galati, Joseph; Person, John; De La Torre, Andrew; Ravendhran, Natarajan; Mushahwar, Andria; O'Leary, Jacqueline; Lee, William; Lawitz, Eric; Ankoma‐Sey, Victor; King, John; Pound, David; Scarsella, Anthony; Thuluvath, Paul; Pockros, Paul; Mailliard, Mark; Shiffman, Mitchell; Sylvestre, Diana; Heiman, David; Jacobson, Ira; Bacon, Bruce; Dimitroff, James; Reindollar, Robert; Tobias, Hillel; Godofsky, Eliot; Rodriguez‐Torres, Maribel; Bennett, Michael; Ben‐Zvi, Jeffrey; Van, Kinh Nguyen; Dao, Long; Huu, Hoang Bui; Minh, Yen Lam; Le Thanh, Ly; Van Long, Dao;
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 42:Issue 7(2015)
• Page Start: 829
• Page End: 844
• Publication Date: 2015-08-04
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.13342
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt13342-abs-0001"> <title>Summary</title> <sec id="apt13342-sec-0001" sec-type="section"> <title>Background</title> <p>Alisporivir (ALV) is an oral, host‐targeting agent with pangenotypic anti‐hepatitis C virus (HCV) activity and a high barrier to resistance.</p> </sec> <sec id="apt13342-sec-0002" sec-type="section"> <title>Aim</title> <p>To evaluate efficacy and safety of ALV plus peginterferon‐α2a and ribavirin (PR) in treatment‐naïve patients with chronic HCV genotype 1 infection.</p> </sec> <sec id="apt13342-sec-0003" sec-type="section"> <title>Methods</title> <p>Double‐blind, randomised, placebo‐controlled, Phase 3 study evaluating ALV 600 mg once daily [response‐guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.</p> </sec> <sec id="apt13342-sec-0004" sec-type="section"> <title>Results</title> <p>A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT <italic>IL28B</italic>). Addition of ALV to PR improved virological response in a dose‐dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.</p> </sec> <sec id="apt13342-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment‐naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon‐free combination regimens.</p> </sec> </abstract>