The 47th Annual Meeting of the European Association for the Study of the Liver (EASL), also called the International Liver Congress, will be held in Barcelona, Spain, April 18 – 22, 2012.

As was the case at the time of our last HCV update report, the most exciting developments have involved interferon-free treatment regimens. This is a key area of interest due to the marginally acceptable side effect profile of interferon and the extended period to which patients are exposed to interferon in currently available treatment regimens. As of this date, at least three interferon-free treatment regimens have demonstrated efficacy sufficient for use in one or more key patient subgroups. Importantly, data disclosed in the EASL abstracts provides new insights into the design criteria for successful interferon-free combinations, and into the likely success of agents currently in development for which little or no data have yet been reported.

This preview provides an overview of the hepatitis C direct acting antiviral (DAA) pipeline, along with efficacy and major safety points for drugs in development. Highlights from the report include:

• Abbott has provided the details of their previously reported success with an interferon-free treatment regimen consisting of the ritonavir-boosted protease inhibitor ABT-450, a non-nucleoside polymerase inhibitor, and ribavirin. With ABT-333 as the non-nucleoside polymerase inhibitor, the SVR rate in a treatment naïve population of 17 GT-1a and 2 GT-1b patients was 95%. This result is notable not only for its success, but because it demonstrates that a combination of potent direct-acting antivirals which lack a high barrier to resistance development can provide high SVR rates in treatment-naïve patients
• Data in the EASL abstracts and other disclosures since our last report reveal disappointing SVR rates for two interferon-free treatment regimens based on nucleoside HCV polymerase inhibitors.
  • In Gilead’s trial of PSI-7977/ribavirin in prior null responders, very high RVR rates were obtained but almost all of the patients experienced viral relapse upon treatment discontinuation (11% SVR)
  • Moderately disappointing results were also obtained in the INFORM-SVR trial of mericitabine/ritonavir-boosted danoprevir/ribavirin in treatment-naïve patients. The SVR rate was 71% in GT-1b patients, but only 26% in GT-1a. From the data presented, it appears that about 70% of GT-1a patients in this trial who achieved RVR failed to achieve SVR
  • These data suggest that a the incorporation of a single direct acting antiviral with a high barrier to resistance development is not sufficient to provide an interferon-free combination with high SVR rates
• Taken in sum, these data suggest that antiviral potency may be a more important design criteria for interferon-free treatment regimens than previously appreciated. Furthermore, high potency combinations may provide an indirect barrier to resistance development, similar to that seen in HAART therapy of HIV
• Data from a trial of PSI-7977, daclastasvir, +/- ribavirin in treatment-naïve patients remains under embargo, and will become available at the conference. Based on the considerations above and others described in the main text, we expect this regimen to produce SVR in a very high proportion of patients.

We have also included a list of Drug Impact Events from our conference planner at the end of the report. BioMedTracker Drug Impact Events can be accessed via the Advanced Event Search or by clicking the links on the list. To obtain the planner in Excel, please email clientservices@pharmaintel.informa.com or contact your sales representative.

For the full report, please download the PDF version at the top of this page.

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