C Bunchorntavakul1,2, K R Reddy2. 1. Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand. 2. Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract
BACKGROUND: The treatment of hepatitis C virus (HCV) has evolved dramatically after the introduction of direct acting anti-virals. NS5A protein plays an important role in HCV replication and is an attractive target for drug development. AIM: To review clinical studies on the efficacy and safety of direct-acting anti-virals regimens containing daclastavir, an NS5A inhibitor, in the treatment of chronic hepatitis C. METHODS: A Medline search was undertaken to identify relevant literature using search terms including 'daclatasvir', 'HCV treatment' and 'NS5A inhibitors'. Furthermore, we scanned abstracts presented at the recent international meetings in liver disease, viral hepatitis and infectious disease, as well as the reference lists of the review articles to identify publications not retrieved by electronic searches. RESULTS: Daclatasvir is the first-in-class HCV NS5A inhibitor that has been demonstrated in Phase I-III trials to have a potent anti-viral effect and clinical efficacy across multiple HCV genotypes (GT). Daclastavir is generally safe and well tolerated, with a low barrier to resistance and low potential for drug-drug interaction. When Daclastavir is added to PEG-IFN/RBV platform, sustained virological response (SVR) rates are increased significantly compared with PEG-IFN/RBV alone. The all-oral combination of Daclastavir/asunaprevir (ASV; protease inhibitor) has high SVR rates against GT1b, but less activity against GT1a. Dual combination of Daclastavir/Sofosbuvir (SOF; nucleotide polymerase inhibitor) and triple combination of Daclastavir/ASV/beclabuvir (BCV; non-nucleoside polymerase inhibitor) have demonstrated >90% SVR rates in both treatment naïve and treatment-experienced patients with GT1. Furthermore, Daclastavir/SOF combination has also demonstrated up to 90% SVR rates in patients with GT3, and in those with human immunodeficiency virus coinfection, cirrhosis and post-transplant HCV recurrence with any GT. Daclastavir/ASV/BCV has primarily demonstrated near 100% SVR rates in patients with GT4. CONCLUSION: Daclastavir-containing regimens, with or without PEG-IFN, have shown promising results in clinical trials, and present an excellent treatment option for those with chronic HCV and for multiple genotypes.
BACKGROUND: The treatment of hepatitis C virus (HCV) has evolved dramatically after the introduction of direct acting anti-virals. NS5A protein plays an important role in HCV replication and is an attractive target for drug development. AIM: To review clinical studies on the efficacy and safety of direct-acting anti-virals regimens containing daclastavir, an NS5A inhibitor, in the treatment of chronic hepatitis C. METHODS: A Medline search was undertaken to identify relevant literature using search terms including 'daclatasvir', 'HCV treatment' and 'NS5A inhibitors'. Furthermore, we scanned abstracts presented at the recent international meetings in liver disease, viral hepatitis and infectious disease, as well as the reference lists of the review articles to identify publications not retrieved by electronic searches. RESULTS:Daclatasvir is the first-in-class HCV NS5A inhibitor that has been demonstrated in Phase I-III trials to have a potent anti-viral effect and clinical efficacy across multiple HCV genotypes (GT). Daclastavir is generally safe and well tolerated, with a low barrier to resistance and low potential for drug-drug interaction. When Daclastavir is added to PEG-IFN/RBV platform, sustained virological response (SVR) rates are increased significantly compared with PEG-IFN/RBV alone. The all-oral combination of Daclastavir/asunaprevir (ASV; protease inhibitor) has high SVR rates against GT1b, but less activity against GT1a. Dual combination of Daclastavir/Sofosbuvir (SOF; nucleotide polymerase inhibitor) and triple combination of Daclastavir/ASV/beclabuvir (BCV; non-nucleoside polymerase inhibitor) have demonstrated >90% SVR rates in both treatment naïve and treatment-experienced patients with GT1. Furthermore, Daclastavir/SOF combination has also demonstrated up to 90% SVR rates in patients with GT3, and in those with human immunodeficiency virus coinfection, cirrhosis and post-transplant HCV recurrence with any GT. Daclastavir/ASV/BCV has primarily demonstrated near 100% SVR rates in patients with GT4. CONCLUSION:Daclastavir-containing regimens, with or without PEG-IFN, have shown promising results in clinical trials, and present an excellent treatment option for those with chronic HCV and for multiple genotypes.
Authors: Jim Young; Nina Weis; Harald Hofer; William Irving; Ola Weiland; Emiliano Giostra; Juan Manuel Pascasio; Lluis Castells; Martin Prieto; Roelien Postema; Cinira Lefevre; David Evans; Heiner C Bucher; Jose Luis Calleja Journal: BMC Infect Dis Date: 2017-01-07 Impact factor: 3.090
Authors: Ossama A Ahmed; Mohamed A Elsebaey; Mohamed Hassan A Fouad; Heba Elashry; Ahmed I Elshafie; Ahmed A Elhadidy; Noha E Esheba; Mohammed H Elnaggar; Shaimaa Soliman; Sherief Abd-Elsalam Journal: Infect Drug Resist Date: 2018-03-28 Impact factor: 4.003
Authors: Paul Kwo; Michael W Fried; K Rajender Reddy; Consuelo Soldevila-Pico; Saro Khemichian; Jama Darling; Phillippe J Zamor; Andrew A Napoli; Beatrice Anduze-Faris; Robert S Brown Journal: Hepatol Commun Date: 2018-02-27