Next Generation Direct-acting Antiviral Agents for Hepatitis C Treatment

Paul Y. Kwo, MD, Marco Lacerda, MD

Abstract


Sofosbuvir in combination with peginterferon and ribavirin for 12 weeks is a new treatment paradigm with a 12 week course of therapy leading to high sustained response rates in genotype 1 and 4  infected individuals including high sustained response rates in cirrhotic patients.  In addition, genotype 2 and 3 infected individuals now have an all oral regimen of sofosbuvir and ribavirin, which is highly effective in all genotype 2 infected individuals with 12 weeks of therapy.  For genotype 3 infected individuals, 24 weeks of the sofosbuvir  and ribavirin leads to high sustained virological response rates in most  groups.  However, cirrhotic genotype 3 infected individuals are going to require additional strategies to optimize SVR rates. It is expected that 2014 should see the presentation of phase 3 data with a variety of combinations of direct acting antiviral agents with the anticipated approval of these combinations occurring in late 2014 or early 2015.  Moreover, one should expect that SVR rates above 90% for treatment naive and treatment failure patients should be the expected norm for all patients.

Keywords


hepatitis C, antiviral, genotype 1 treatment, Sofosbuvir, peginterferon, ribavirin

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References


Centers for Disease Control and Prevention. Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965. MMWR Recomm Rep. 2012;61(RR-4):1-32.

Manns M, Marcellin P, Fred Poordad F, et al. 1413 SIMEPREVIR (TMC435) WITH Peginterferon/Ribavirin For Treatment Of Chronic Hcv Genotype-1 Infection In Treatment-Naïve Patients: Results From Quest-2, A Phase Iii Trial. J Hepatol. 2013;58:S568.

Jacobson I, Dore G, Foster G. Simeprevir (TMC435) with peginterferon/ribavirin for chronic hCV genotype 1 infection in treatment-naïve patients: results from QUEST-1, a Phase III trial. Reported in the 48th Annual Meeting of the European Association for the Study of the Liver; 2013.

Kowdley KV, Lawitz E, Crespo I, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet. 2013;381(9883):2100-2107.

Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878-1887.

Gane EJ, Stedman CA, Hyland RH, et al. Efficacy of Nucleotide Polymerase Inhibitor Sofosbuvir Plus the NS5A Inhibitor Ledipasvir or the NS5B Non-Nucleoside Inhibitor GS-9669 Against HCV Genotype 1 Infection. Gastroenterology.

Gane EJ, Stedman CA, Hyland RH, et al. Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C. N Engl J Med. 2013;368(1):34-44.

Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet.

Jacobson I, Ghalib R, Rodriguez-Torres M, et al. SVR results of a once-daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naïve and prior null responder patients: The COSMOS study. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013). Washington, DC. 2013;1-5.

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):211-221.

Kowdley KV, Lawitz E, Poordad F, et al. 3 Safety And Efficacy Of Interferon-Free Regimens Of Abt-450/R, Abt-267, Abt-333 +/− Ribavirin In Patients With Chronic HCV Gt1 Infection: Results From The Aviator Study. J Hepatl. 2013;58:S2.

Chayama K, Suzuki Y, Ikeda K, et al. All-Oral Combination of Daclatasvir Plus Asunaprevir in Interferon-Ineligible Naive/Intolerant and Nonresponder Japanese Patients Chronically Infected With HCV Genotype 1b: Results From a Phase 3 Trial. 64th Annual Meeting of the American Association for the Study of Liver diseases; 2013.

Lawitz E, Varunok P, Thuluvath PJ, et al. Interferon- and Ribavirin-free Regimen of ABT- 450/r + ABT-267 in HCV Genotype 1b-infected Treatment-naïve Patients and Prior Null Responders. Hepatology. 2013;58(1):75.

Zeuzem S, Soriano V, Asselah T, et al. Faldaprevir and Deleobuvir for HCV Genotype 1 Infection. N Engl J Med. 2013;369(7):630-639.

Everson GT, Sims KD, Thuluvath PJ, et al. Phase 2b study of the interferon-free and ribavirin-free combination of daclatasvir, asunaprevir, and BMS-791325 for 12 weeks in treatment-naive patients with chronic HCV genotype 1 infection. 64th Annual Meeting of the American Society for the Study of Liver Diseases (AASLD). Washington, DC. 2013.

Lawitz E, Vierling J, Murillo A. High Efficacy and Safety of the All-Oral Combination Regimen. 2013: MK-5172/MK-8742±RBV for 12 weeks in HCV genotype 1 infected patients: the C-WORTHY study. Program and abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases.

Gane EJ, Stedman CA, Hyland RH, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med 2013;368(1):34-44.

Zeuzem S, Dusheiko G, Riina Salupere R. Sofosbuvir+ ribavirin for 12 or 24 weeks for patients with HCV genotype 2 or 3: the VALENCE Trial. 64th Annual Meeting of the American Association for the Study of Liver Diseases; 2013. 1-5.


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