Jules Levin from NATAP at the Copenhagen conference

I just arrived in Copenhagen early this morning for the EASL liver meeting. The conference organizers always do a very nice job with this conference. The outgoing president of EASL, Dr Jean-Michel Pawlotsky, has done a very nice job of making this conference a great meeting. This meeting is where you will see all the new data for new drugs reported this year and in the future, it is a comfortable well organized meeting, well planned and has become very important. There are 25 new HCV drugs being presented here, many of which are listed below. Currently in development are are 7 HCV protease inhibitors, 16 polymerase inhibitors, the first NS5A inhibitor which looked very good in phase 1 at AASLD in Nov 2008, a new interferon (lambda) which may not have interferon side effects, 2 entry inhibitors, 3 cyclophilin inhibitors, and intravenous administered silimarin. As you may know Vertex's telaprevir and Sch ering's boceprevir are 2 protease inhibitors now in phase III so they are expected to be FDA reviewed and be available in the latter half of 2010. They will be used with peginterferon+ribavirin and for treatment-naive genotype 1 duration of therapy will initially be 24 weeks for telaprevir and for boceprevir it looks like 24 weeks but they are also looking at 48 weeks. For previous null responders and 48 weeks telaprevir may be shown to be preferable, this is uncertain now. The SVR rates in phase 2 are about 65% for telaprevir in naives and 40% in null responders and much higher than the 40% in relapsers and breakthroughs. For boceprevir SVR rates were about 55% in naives. Results from ongoing phase III are not yet available but there will be new phase II data here at EASL for both drugs. HCV drug resistance is an important concern, more than HIV drug resistance. Drug resistance to HCV protease inhibitors can occur very quickly, as soon as within a few days after starting th erapy, so this is a very important issue to consider. Using peginter feron plus ribavirin can prevent resistance to the oral drug but it can still occur. When a 2nd oral drug will be added to the regimen of course this will further reduce the possibility of developing drug resistance. I expect there will be quite a lot of discussion about resistance over the next 2 years. The preliminary data looks good for all the other drugs but they are all in early development in studies in patients so we need more time to see how they progress through additional studies. My expectation is that in several years after boceprevir & telaprevir are approved we will have a regimen with 2 oral drugs (1 protease and 1 other drug) plus peginterferon and ribavirin, and SVR rates will be 80% in genotype 1 naives with 24 weeks therapy, and for African-Americans the SVR rate should be lower but still good. There is no data from phase II in African-Americans but both phase III studies are enrolling African-Americans and will provide data. When we are able to combin e 3 oral drugs with peginterferon plus ribavirin I expect SVR rates around 90% and perhaps higher for genotype 1 naives and a little lower for African-Americans. We will eventually approach curing everyone. When will this happen? The other classes of HCV drugs are either in early phase II now are about to begin phase II studies so it could take about 3 years for phase II and phase III. Some would say I am being optimistic regarding the timeframe, but regardless I expect this to happen.
Jules Levin, NATAP