Abstract
Daclatasvir (Daklinza®), an inhibitor of hepatitis C virus (HCV) NS5A protein, is an oral, direct-acting antiviral with potent pangenotypic activity that approved in many countries worldwide. In the EU, it is approved for use in combination with other drugs for the treatment of chronic HCV genotype 1, 3 or 4 infection. Daclatasvir produces high sustained virological response rates in patients chronically infected with HCV genotypes 1–4 when used in combination with peginterferon-α + ribavirin or in combination with sofosbuvir (± ribavirin). Daclatasvir has a moderately high genetic barrier to resistance, is effective during short-term treatment over 12 weeks, has a safety and tolerability profile similar to that of placebo, has a relatively low potential for drug interactions, and is not associated with clinically relevant drug interactions with drugs commonly used in patients with HCV, including other antivirals and transplant medications.
Similar content being viewed by others
References
World Health Organization. Hepatitis C: fact sheet no. 164. 2014. http://www.who.int/mediacentre/factsheets/fs164/en/#. Accessed 21 Nov 2015.
European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol. 2015;63(1):199–236.
Ashfaq UA, Javed T, Rehman S, et al. An overview of HCV molecular biology, replication and immune responses. Virol J. 2011;8:161.
European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60(2):392–420.
Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461(7262):399–401.
Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461(7265):798–801.
Daklinza (daclatasvir dihydrochloride): summary of product characteristics. London: European Medicines Agency; 2015.
Daklinza (daclatasvir dihydrochloride) tablet: US prescribing information. Princeton: Bristol-Myers Squibb Company; 2015.
Gao M, Nettles RE, Belema M, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature. 2010;465(7294):96–100.
Guedj J, Dahari H, Rong L, et al. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci USA. 2013;110(10):3991–6.
Pelosi LA, Voss S, Liu M. Effect on hepatitis C virus replication of combinations of direct-acting antivirals, including NS5A inhibitor daclatasvir. Antimicrob Agents Chemother. 2012;56:5230–9.
Fridell RA, Qiu D, Wang C, et al. Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob Agents Chemother. 2010;54(9):3641–50.
Fridell RA, Wang C, Sun JH, et al. Genotypic and phenotypic analysis of variants resistant to hepatitis C virus nonstructural protein 5A replication complex inhibitor BMS-790052 in humans: in vitro and in vivo correlations. Hepatology. 2011;54(6):1924–35.
Wang C, Jia L, O’Boyle DR 2nd, et al. Comparison of daclatasvir resistance barriers on NS5A from hepatitis C virus genotypes 1 to 6: implications for cross-genotype activity. Antimicrob Agents Chemother. 2014;58(9):5155–63.
Bifano M, Hwang C, Oosterhuis B, et al. Assessment of pharmacokinetic interactions of the HCV NS5A replication complex inhibitor daclatasvir with antiretroviral agents: ritonavir-boosted atazanavir, efavirenz and tenofovir. Antivir Ther. 2013;18(7):931–40.
Garimella T, Gandhi Y, Wang R, et al. Daclatasvir exposure alone does not explain HCV relapse in HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir with ritonavir-boosted darunavir in the ALLY-2 study [abstract no. 728]. Hepatology. 2015;62(6 Suppl):572A.
Gandhi Y, Adamcyzk R, Wang R, et al. Assessment of drug-drug interactions between daclatasvir and darunavir/ritonavir or lopinavir/ritonavir [poster no. 80]. In: 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy; 2015.
Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015;61(4):1127–35.
Leroy V, Angus PW, Bronowicki J-P, et al. All-oral treatment with daclatasvir (DCV) plus sofosbuvir (SOF) plus ribavirin (RBV) for 12 or 16 weeks in HCV genotype (GT) 3-infected patients with advanced fibrosis or cirrhosis: the ALLY-3+ phase 3 study [abstract no. LB-3]. Hepatology. 2015:62(6 Suppl):1380A–1381A.
Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370(3):211–21.
Jacobson I, Zeuzem S, Flisiak R, et al. Daclatasvir vs telaprevir in combination with peginterferon alfa/ribavirin in treatment-naive patients with HCV genotype 1: phase 3 COMMAND-3 results [abstract no. 0213]. J Viral Hepat. 2014;21(Suppl S2):7–8.
Hézode C, Alric L, Brown A, et al. Randomized controlled trial of the NS5A inhibitor daclatasvir plus peginterferon and ribavirin for HCV genotype-4 (COMMAND-4). Antivir Ther. 2015. doi:10.3851/IMP2985.
Hézode C, Hirschfield GM, Ghesquiere W, et al. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study. Gut. 2014;64(6):948–56.
Izumi N, Yokosuka O, Kawada N, et al. Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1. Antivir Ther. 2014;19(5):501–10.
Pol S, Ghalib RH, Rustgi VK, et al. Daclatasvir for previously untreated chronic hepatitis C genotype-1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trial. Lancet Infect Dis. 2012;12(9):671–7.
Suzuki F, Toyota J, Ikeda K, et al. A randomized trial of daclatasvir with peginterferon alfa-2b and ribavirin for HCV genotype 1 infection. Antivir Ther. 2014;19(5):491–9.
Dore GJ, Lawitz E, Hézode C, et al. Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection. Gastroenterology. 2015;148(2):355–66.e1.
Ratziu V, Gadano A, Pol S, et al. Triple therapy with daclatasvir (DCV; BMS-790052), peginterferon alfa-2a and ribavirin in HCV-infected prior null and partial responders: 12-week results of phase 2b COMMAND-2 trial [abstract no. 1207, plus poster presented at the 47th Annual Meeting of the European Association for the Study of the Liver, 2012]. J Hepatol. 2012;56(Suppl 2):S478–9.
US National Institutes of Health. ClinicalTrials.gov. 2015. http://clinicaltrials.gov/. Accessed 30 Nov 2015.
Manns M, Pol S, Jacobson IM, et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet. 2014;384(9954):1597–605.
Jensen D, Sherman KE, Hézode C, et al. Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders. J Hepatol. 2015;63(1):30–7.
Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714–25.
McCormack PL. Daclatasvir: a review of its use in adult patients with chronic hepatitis C virus infection. Drugs. 2015;75(5):515–24.
Acknowledgments
The review was updated from Drugs 2015; 75(5):515–24 [33], and was reviewed by: A. Antonelli, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; F. Araujo, Faculty of Experimental Sciences, Pablo de Olavide University, Seville, Spain; F. Bessone, Department of Gastroenterology and Hepatology, University of Rosario School of Medicine, Rosario, Argentina; S. Mirkov, Auckland, New Zealand; S. Saluja, Saran Ashram Hospital, Dayalbagh, Agra, India. During the peer review process, the manufacturer of daclatasvir was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
The preparation of this review was not supported by any external funding.
Conflicts of interest
P. L. McCormack and K. A. Lyseng-Williamson are salaried employees of Adis/Springer, are responsible for the article content and declare no conflicts of interest.
Rights and permissions
About this article
Cite this article
McCormack, P.L., Lyseng-Williamson, K.A. Daclatasvir in hepatitis C virus infection: a guide to its use in the EU. Drugs Ther Perspect 32, 42–49 (2016). https://doi.org/10.1007/s40267-015-0272-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40267-015-0272-3