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EASL 2013: International Liver Congress Kicks Off with Hep C New Drug Highlights

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The EASL International Liver Congress is now underway at the Amsterdam RAI congress center. At a Wednesday press conference, EASL officials gave a preview of some of the hepatitis C treatment highlights -- both augmentation of interferon-based therapy and interferon-free regimens -- to be presented at the meeting, which runs through Sunday.

The annual meeting of the European Association for the Study of the Liver is one of the key annual scientific meetings covering hepatitis B and C and its complications, bringing together leading researchers from around the world.

The rapidly evolving hepatitis C drug development pipeline continues to be a major focus this year, as the advent of direct-acting antiviral agents (DAAs) has changed the treatment paradigm. Most of the new drugs were first studied as additions to interferon-based therapy -- with several such trials being presented here -- and that is how they will likely be initially used in clinical practice. But many patients and providers eagerly await all-oral, interferon-free regimens.

EASL Secretary General Mark Thursz presented highlights of several DAA studies to be presented over the next 4 days:

  • Daclatasvir all oral -- An interferon-free regimen of NS5A inhibitor daclatasvir (formerly BMS-790052), protease inhibitor asunaprevir (formerly BMS-650032), and polymerase inhibitor BMS-791325 produced SVR rates exceeding 90% for treatment-naive genotype 1 patients. Another study showed daclatasvir + sofosbuvir is a potential rescue regimen for people who are not cured with standard-of-care triple therapy using approved HCV protease inhibitors.
  • Faldaprevir (formerly BI 201335) -- the STARTVerso 1 trial produced an overall 88% SVR12 rate for treatment-naive genotype 1 patients in Europe and Japan using faldaprevir plus pegylated interferon/ribavirin.
  • Simeprevir (formerly TMC435) -- the QUEST-1 (U.S.) and QUEST-2 (European) studies of simeprevir plus pegylated interferon/ribavirin for treatment-naive genotype 1 patients showed 12-week post-treatment SVR (SVR12) rates of approximately 80%, mostly with 24 weeks of therapy.
  • Sofosbuvir (formerly GS-7977) -- Researchers will present findings from a series of Gilead studies including FISSION and FUSION (sofosbuvir plus ribavirin for treatment-naive and treatment-experienced genotype 2/3 patients), POSITRON (sofosbuvir plus ribavirin for people with genotype 2/3 who are ineligible for, intolerant of, or unwilling to take interferon), and NEUTRINO (sofosbuvir plus pegylated interferon/ribavirin for treatment-naive patients with genotypes 1,4,5, and 6). Across the board, sustained virological response (SVR) rates were high and sofosbuvir was well-tolerated.
  • AbbVie all-oral -- the AVIATOR study showed that interferon-free regimens including the HCV protease inhibitor ABT-450, polymerase inhibitor ABT-333, and NS5A inhibitor ABT-267, with or without ribavirin, produced SVR rates exceeding 90% for treatment-naive and previously treated genotype 1 patients.

Experts expect that the first next-generation DAAs may be approved as early as the end of 2013, at least for easier-to-treat patients. Janssen recently announced that it has submitted requests to the U.S. Food and Drug Administration (FDA) and European Medicines Agency for approval of simeprevir, and Gilead requested FDA approval of sofosbuvir in early April.

Overall, Thursz characterized the latest DAA results as "very encouraging," but cautioned that studies to date have looked at limited numbers of patients. "I'm excited to see what happens in Phase 3, but we're not there yet," he said.

One issue that has come up in recent trials is the mismatch in effectiveness for people with genotype 2 and genotype 3. While these patients are often considered as a single group, analysis of more study participants has shown that they respond quite differently to some DAAs. As also happened with HCV subtypes 1a and 1b, evidence increasingly indicates that these populations should be regarded as separate in trials and clinical practice.

EASL Scientific Committee member Laurent Castera presented findings showing that people with advanced disease can be effectively treated with the currently approved DAAs boceprevir (Victrelis) or telaprevir (Incivek or Incivo) plus pegylated interferon/ribavirin, but they must be monitored carefully for adverse events including potentially fatal infections. Both Castera and Thursz noted that next-generation DAAs are much better tolerated as part of interferon-based triple therapy, and predicted that once they are approved the first 2 HCV protease inhibitors will fall by the wayside.

In addition to hepatitis C treatment news, Liver Congress attendees will also hear new information about hepatitis B and delta, hepatocellular carcinoma, liver transplantation, and other types of liver disease.

Look for HIVandHepatitis.com's breaking news coverage starting Thursday at www.HIVandHepatitis.comand via @HIVandHepatitis on Twitter.  Abstracts and other information are available on the conference web site at http://www2.kenes.com/liver-congress/pages/home.aspx for abstracts and other content.

4/24/13

References

GT Everson et al. Interim analysis of an interferon (IFN)- and ribavirin (RBV)-free regimen of daclatasvir (DCV), asunaprevir (ASV), and BMS-791325 in treatment-naive, hepatitis C virus genotype 1-infected patients. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1423.

P Ferenci et al. Faldaprevir plus pegylated interferon alfa-2a and ribavirin in chronic HCV genotype-1 treatment-naive patients: final results from STARTVerso 1, a randomised, double-blind, placebo-controlled phase III trial. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1416.

H Fontaine. SVR12 rates and safety of triple therapy including telaprevir or boceprevir in 221 cirrhotic non responders treated in the French early access program (ANRS CO20-CUPIC). Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 60.

E Gane et al. Phase 3 randomized controlled trial of all-oral treatment with sofosbuvir+ribavirin for 12 weeks compared to 24 weeks of peg+ribavirin in treatment-naive GT2/3 HCV-infected patients (FISSION). 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 5.

E Gane et al. All-oral sofosbuvir-based 12-week regimens for the treatment of chronic HCV infection: the ELECTRON study. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 14.

I Jacobson et al. Simeprevir (tmc435) with peginterferon/ribavirin for chronic HCV genotype-1 infection in treatment-naive patients: results from QUEST-1, a phase III trial. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1425.

I Jacobson et al. Treatment with sofosbuvir+ribavirin for 12 weeks achieves SVR12 of 78% in GT2/3 interferon-ineligible, -intolerant, or -unwilling patients: results of the phase 3 POSITRON trial. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 61.

K Kowdley et al. 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. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 3.

E Lawitz et al. Sofosbuvir + peginterferon + ribavirin for 12 weeks achieves 90% SVR12 in genotype 1, 4, 5, or 6 HCV infected patients: the NEUTRINO study. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1411.

M Manns et al. Simeprevir (tmc435) with peginterferon/ribavirin for treatment of chronic HCV genotype-1 infection in treatment-naive patients: results from QUEST-2, a phaseIII trial. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1413.

DR Nelson et al. All oral therapy with sofosbuvir+ribavirin for 12 or 16 weeks in treatment experienced GT/3 HCV-infected patients: results of the phase 3 fusion trial. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 6.

K Rutter. Safety of triple therapy with telaprevir or boceprevir in hepatitis C patients with advanced liver disease - predictive factors for sepsis. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 65.

MS Sulkowski et al. Sustained virologic response with daclatasvir plus sofosbuvir +/- ribavirin (RBV) in chronic HCV genotype (GT) 1-infected patients who previously failed telaprevir (TVR) or boceprevir (BOC). 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 1417.