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Daclatasvir + Asunaprevir: First Global Approval

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Abstract

The combination of daclatasvir + asunaprevir [Daklinza® + Sunvepra® (Japan)], two direct-acting antiviral agents, has been developed by Bristol–Myers Squibb for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 infections, including those with compensated cirrhosis. Daclatasvir + asunaprevir has received its first global approval in this indication in Japan. Daclatasvir + asunaprevir is the first all-oral, interferon- and ribavirin-free regimen for this indication. This article summarizes the milestones in the development of daclatasvir + asunaprevir leading to this first approval for the treatment of chronic HCV genotype 1 infections.

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References

  1. Gonzalez SA. Management of recurrent hepatitis C following liver transplantation. Gastroenterol Hepatol. 2010;6(10):637–45.

    Google Scholar 

  2. Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45(4):529–38.

    Article  PubMed  Google Scholar 

  3. Gottwein JM, Jensen SB, Li Y-P, et al. Combination treatment with hepatitis C virus protease and NS5A inhibitors is effective against recombinant genotype 1a, 2a, and 3a viruses. Antimicrob Agents Chemother. 2013;57(3):1291–303.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Shah N, Pierce T, Kowdley KV. Review of direct-acting antiviral agents for the treatment of chronic hepatitis C. Expert Opin Investig Drugs. 2013;22(9):1107–21.

    Article  CAS  PubMed  Google Scholar 

  5. Wendt A, Adhoute X, Castellani P, et al. Chronic hepatitis C: future treatment. Clin Pharmacol. 2014;6:1–17.

    PubMed Central  PubMed  Google Scholar 

  6. Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335–74.

    Article  CAS  PubMed  Google Scholar 

  7. Ghany MG, Nelson DR, Strader DB, et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54(4):1433–44.

    Article  PubMed Central  PubMed  Google Scholar 

  8. European Association for the Study of the L. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2011;55(2):245–64.

    Article  Google Scholar 

  9. Chae HB, Park SM, Youn SJ. Direct-acting antivirals for the treatment of chronic hepatitis C: open issues and future perspectives. Sci World J. 2013;2013:704912.

    Article  Google Scholar 

  10. De Clercq E. Current race in the development of DAAs (direct-acting antivirals) against HCV. Biochem Pharmacol. 2014;89(4):441–52.

    Article  PubMed  Google Scholar 

  11. Martel-Laferrière V, Bichoupan K, Dieterich D. Interferon-free regimens for hepatitis C: combine and conquer. BioDrugs. 2014;28(2):161–9.

    Article  PubMed  Google Scholar 

  12. Lange CM, Zeuzem S. Perspectives and challenges of interferon-free therapy for chronic hepatitis C. J Hepatol. 2013;58(3):583–92.

    Article  CAS  PubMed  Google Scholar 

  13. Stedman CAM. Current prospects for interferon-free treatment of hepatitis C in 2012. J Gastroenterol Hepatol. 2013;28(1):38–45.

    Article  CAS  PubMed  Google Scholar 

  14. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975–82.

    Article  CAS  PubMed  Google Scholar 

  15. Kramer JR, Kanwal F, Richardson P, et al. Gaps in the achievement of effectiveness of HCV treatment in national VA practice. J Hepatol. 2012;56(2):320–5.

    Article  PubMed  Google Scholar 

  16. Ferenci P. Treatment of chronic hepatitis C–are interferons really necessary? Liver Int. 2012;32(Suppl 1):108–12.

    Article  CAS  PubMed  Google Scholar 

  17. Pockros PJ. Interferon-free hepatitis C therapy: how close are we? Drugs. 2012;72(14):1825–31.

    Article  CAS  PubMed  Google Scholar 

  18. Dubuisson J. Hepatitis C virus proteins. World J Gastroenterol. 2007;13(17):2406–15.

    Article  CAS  PubMed  Google Scholar 

  19. Pockros PJ. New direct-acting antivirals in the development for hepatitis C virus infection. Ther Adv Gastroenterol. 2010;3(3):191–202.

    Article  CAS  Google Scholar 

  20. Asselah T, Marcellin P. Interferon free therapy with direct acting antivirals for HCV. Liver Int. 2013;33:93–104.

    Article  CAS  PubMed  Google Scholar 

  21. Pawlotsky JM, Chevaliez S, McHutchison JG. The hepatitis C virus life cycle as a target for new antiviral therapies. Gastroenterology. 2007;132(5):1979–98.

    Article  CAS  PubMed  Google Scholar 

  22. Sulkowski M, Gardiner D, 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.

    Article  CAS  PubMed  Google Scholar 

  23. Bristol–Myers Squibb. Japan approves first all-oral, interferon- and ribavirin-free hepatitis C treatment, Daklinza® (daclatasvir) and Sunvepra® (asunaprevir) Dual Regimen [media release]. 7 July 2014 http://news.bms.com/press-release/japan-approves-first-all-oral-interferon-and-ribavirin-free-hepatitis-c-treatment-dakl.

  24. Bristol–Myers Squibb Company. Daklinza Tablets (tavaborole) Japanese Prescribing Information. 2014.

  25. Bristol–Myers Squibb Company. Sunvepra Capsules (asunaprevir) Japanese Prescribing Information. 2014.

  26. Bristol–Myers Squibb Company. Bristol–Myers Squibb Submits NDAs for Daclatasvir and Asunaprevir to US FDA for the Treatment of Hepatitis C. [media release]. 2014. http://www.bms.com.

  27. Bristol–Myers Squibb. Bristol–Myers Squibb Receives U.S. FDA Breakthrough therapy designation for all-oral daclatasvir dual investigational regimen for chronic hepatitis C [media release]. 24 Feb 2014. http://news.bms.com/press-release/bristol-myers-squibb-receives-us-fda-breakthrough-therapy-designation-all-oral-daclata.

  28. Bristol–Myers Squibb. Bristol–Myers Squibb Receives Positive CHMP Opinion for Daklinza® (daclatasvir) for Treatment of Chronic Hepatitis C in the European Union [media release]. 27 June 2014. http://news.bms.com/press-release/bristol-myers-squibb-receives-positive-chmp-opinion-daklinza-daclatasvir-treatment-chr.

  29. United States securities and exchange commission. Form 10-K: annual report pursuant to section 13 OR 15(d) of the securities exchange act of 1934 for the fiscal year ended December 31, 2012. Commission File Number 1–1136 (Bristol–Myers Squibb Company). 2013. http://www.sec.gov/Archives/edgar/data/14272/000119312513061678/d450621d10k.htm. Accessed 22 July 2014.

  30. McPhee F, Toyota J, Chayama K, et al. Analysis of HCV resistance variants in a phase 3 trial of daclatasvir combined with asunaprevir for Japanese patients with genotype 1b infection. Hepatology. 2013;58(4 suppl 1):749A.

  31. McPhee F, Hernandez D, Yu F, et al. Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir. Hepatology. 2013;58(3):902–11.

    Article  CAS  PubMed  Google Scholar 

  32. Karino Y, Toyota J, Ikeda K, et al. Characterization of virologic escape in hepatitis C virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevir. J Hepatol. 2013;58(4):646–54.

    Article  CAS  PubMed  Google Scholar 

  33. Kosaka K, Imamura M, Hayes CN, et al. Emergence of resistant variants detected by ultra-deep sequencing after asunaprevir and daclatasvir combination therapy in patients infected with hepatitis C virus genotype 1. J Viral Hepat. 2014;. doi:10.1111/jvh.12271.

    PubMed  Google Scholar 

  34. McPhee F, Hernandez D, Zhou N, et al. Comparison of pre-existing and emerging resistance-associated variants in US, EU and Japanese HCV genotype 1b prior interferon alfa (IFN-alpha) non responders and IFN-alpha ineligible patients treated with daclatasvir and asunaprevir. Hepatology. 2012;56:559A–60A.

    Google Scholar 

  35. Bifano M, Sevinsky H, Bedford BR, et al. Co-Administration of Bms-790052 and Bms-650032 does not result in a clinically meaningful pharmacokinetic interaction in healthy subjects [abstract no. 827]. In: 61st Annual Meeting of the American Association for the Study of Liver Diseases; 29 Oct–02 Nov 2010; Boston.

  36. Chan P, Tafoya E, Eley T, et al. Exposure-response analyses of asunaprevir in combination with daclatasvir peginterferon/ ribavirin among patients with genotype 1 chronic Hcv infection: dose selection for phase 3 clinical trials [abstract no. 804]. J Hepatol. 2013;58:S328–9.

    Article  Google Scholar 

  37. Bifano M, Sevinsky H, Hwang C, et al. Effect of the coadministration of daclatasvir on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate. Antivir Ther. 2013. doi:10.3851/IMP2718.

    Google Scholar 

  38. Kumada H, Suzuki Y, Ikeda K, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology. 2014;59(6):2083–91.

    Article  CAS  PubMed  Google Scholar 

  39. 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. doi:10.1016/S0140-6736(14)61059-X.

    Google Scholar 

  40. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216–24.

    Article  CAS  PubMed  Google Scholar 

  41. Lok A, Gardiner D, Hezode C, et al. Confirmation that quadruple therapy with daclatasvir (NS5A inhibitor), asunaprevir (NS3 inhibitor) and peginterferon/ribavirin results in high rate of SVR4 in HCV genotype 1 null responders. J Hepatol. 2012;56:S557.

    Article  Google Scholar 

  42. Suzuki Y, Ikeda K, Suzuki F, et al. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol. 2013;58(4):655–62.

    Article  CAS  PubMed  Google Scholar 

  43. Chayama K, Takahashi S, Toyota J, et al. Dual therapy with the non-structural protein 5A inhibitor, daclatasvir, and the non-structural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders. Hepatology. 2012;55(3):742–8.

    Article  CAS  PubMed  Google Scholar 

  44. Kamae I, Ward T, Webster S, et al. Estimating the long-term clinical effectiveness of daclatasvir plus asunaprevir in Japanese patients chronically infected with HCV genotype 1b: a subgroup analysis. Hepatol Int 2014;8(1 suppl.):S156.

  45. McEwan P, Ward T, Webster S, et al. Estimating the long-term clinical and economic outcomes of daclatasvir plus asunaprevir in difficult-to-treat Japanese patients chronically infected with hepatitis C genotype 1b. Value Health Reg Issues. 2014;3:136–45.

    Article  Google Scholar 

  46. Bristol–Myers Squibb Company. Phase III China GT 1b Interferon (IFN) intolerant prev exclude dual [ClinicalTrials.gov identifier NCT01995266] National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/ct2/show/NCT01995266?term=NCT01995266&rank=1. Accessed 22 July 2014.

  47. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). New treatment response in people with and without cirrhosis from chronic hepatitis C [ClinicalTrials.gov identifier NCT01888900] National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/ct2/show/NCT01888900?term=nct01888900&rank=1. Accessed 22 July 2014.

  48. National Institutes of Health Clinical Center (CC). Safety, tolerability, and efficacy of asunaprevir and daclatasvir in subjects co-infected with HIV-HCV [ClinicalTrials.gov identifier NCT02124044] National Institutes of Health, Clinicaltrials.gov. 2014. http://clinicaltrials.gov/ct2/show/NCT02124044?term=NCT02124044&rank=1. Accessed 22 July 2014.

  49. Bristol–Myers Squibb Company. Three-year follow-up study of subjects who participated in a previous asunaprevir (BMS-650032) and/or daclatasvir (BMS-790052) chronic hepatitis C clinical trial [ClinicalTrials.gov identifier NCT01492504] National Institutes of Health, ClinicalTrials.gov. 2011. http://clinicaltrials.gov/ct2/show/study/NCT01492504?term=NCT01492504&rank=1. Accessed 22 July 2014.

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Disclosure

The preparation of this report was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. R.M. Poole is a contracted employee of Adis, Springer SBM.

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    Raewyn M. Poole

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Correspondence to Raewyn M. Poole.

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This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

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Poole, R.M. Daclatasvir + Asunaprevir: First Global Approval. Drugs 74, 1559–1571 (2014). https://doi.org/10.1007/s40265-014-0279-4

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