Meike H van der Ree1, Adriaan J van der Meer2, Joep de Bruijne1, Raoel Maan2, Andre van Vliet3, Tania M Welzel4, Stefan Zeuzem4, Eric J Lawitz5, Maribel Rodriguez-Torres6, Viera Kupcova7, Alcija Wiercinska-Drapalo8, Michael R Hodges9, Harry L A Janssen10, Hendrik W Reesink11. 1. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. 2. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands. 3. PRA International, Zuidlaren, The Netherlands. 4. J.W. Goethe University Hospital, Frankfurt, Germany. 5. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA. 6. Fundacion de Investigacion, San Juan, Porto Rico. 7. Department of Internal Medicine, Derer's Hospital, University Hospital Bratislava, Slovakia. 8. Medical University of Warsaw, Warsaw Hospital for Infectious Diseases, Warsaw, Poland. 9. Santaris Pharma A/S, San Diego, USA. 10. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands; Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, Canada. 11. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: h.w.reesink@amc.uva.nl.
Abstract
BACKGROUND AND AIMS: MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus (HCV) and promotes HCV RNA accumulation. Decreased intra-hepatic levels of miR-122 were observed in patients with hepatocellular carcinoma, suggesting a potential role of miR-122 in the development of HCC. Miravirsen targets miR-122 and resulted in a dose dependent and prolonged decrease of HCV RNA levels in chronic hepatitis C patients. The aim of this study was to establish the sustained virological response rate to peginterferon (P) and ribavirin (R) following miravirsen dosing and to assess long-term safety in patients treated with miravirsen. METHODS: In this multicenter, retrospective follow-up study we included 36 treatment naïve patients with chronic hepatitis C genotype 1 who receivedfive weekly subcutaneous injections with miravirsen or placebo over a 29-day period in a phase 2a study. Patients were offered PR therapy 3weeks (3mg/kg group) or 6weeks (5 or 7mg/kg group) after completion of miravirsen or placebo dosing. RESULTS:PR therapy was started in 14/36 patients of whom 12 had received miravirsen. SVR was achieved in 7/12 patients previously dosed with miravirsen. All patients dosed with 7mg/kg miravirsen who were subsequently treated with PR achieved SVR. One patient had a prolonged undetectable HCV RNA period from week 14 to week 29 after baseline without subsequent antiviral therapy and relapsed thereafter. None of the patients treated with anti-miR-122 developed HCC or other liver-related complications. CONCLUSION: No long-term safety issues were observed among 27 miravirsen-treated patients. Targeting miR-122 may be an effective and safe treatment strategy for HCV infection and should be investigated in larger clinical trials.
RCT Entities:
BACKGROUND AND AIMS: MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus (HCV) and promotes HCV RNA accumulation. Decreased intra-hepatic levels of miR-122 were observed in patients with hepatocellular carcinoma, suggesting a potential role of miR-122 in the development of HCC. Miravirsen targets miR-122 and resulted in a dose dependent and prolonged decrease of HCV RNA levels in chronic hepatitis Cpatients. The aim of this study was to establish the sustained virological response rate to peginterferon (P) and ribavirin (R) following miravirsen dosing and to assess long-term safety in patients treated with miravirsen. METHODS: In this multicenter, retrospective follow-up study we included 36 treatment naïve patients with chronic hepatitis C genotype 1 who received five weekly subcutaneous injections with miravirsen or placebo over a 29-day period in a phase 2a study. Patients were offered PR therapy 3weeks (3mg/kg group) or 6weeks (5 or 7mg/kg group) after completion of miravirsen or placebo dosing. RESULTS: PR therapy was started in 14/36 patients of whom 12 had received miravirsen. SVR was achieved in 7/12 patients previously dosed with miravirsen. All patients dosed with 7mg/kg miravirsen who were subsequently treated with PR achieved SVR. One patient had a prolonged undetectable HCV RNA period from week 14 to week 29 after baseline without subsequent antiviral therapy and relapsed thereafter. None of the patients treated with anti-miR-122 developed HCC or other liver-related complications. CONCLUSION: No long-term safety issues were observed among 27 miravirsen-treated patients. Targeting miR-122 may be an effective and safe treatment strategy for HCV infection and should be investigated in larger clinical trials.
Authors: T S Worst; K Daskalova; A Steidler; K Berner-Leischner; R Röth; B Niesler; C-A Weis; M C Kriegmair; P Erben; D Pfalzgraf Journal: World J Urol Date: 2017-06-20 Impact factor: 4.226
Authors: Rebecca Johnson Kameny; Youping He; Terry Zhu; Wenhui Gong; Gary W Raff; Cheryl J Chapin; Sanjeev A Datar; Jason T Boehme; Akiko Hata; Jeffrey R Fineman Journal: Am J Physiol Heart Circ Physiol Date: 2018-06-15 Impact factor: 4.733