EASL 45th Annual Meeting (European Association for the Study of the Liver)

rom Jules Levin of NATAP: Everyone with HCV can be cured with all the new HCV drugs being developed. Over 26 new orally administered drugs are at various stages of development with the 1st 2 HCV protease inhibitors to be approved by the FDA in mid-2011. A protease will be used in combination with peg/rbv for at least the near-term future until the study has been conducted that can prove a cure, SVR (sustained viral response) can be achieved by at least some patients without peg or peg/rbv. Within a few years we will have combiations of 2 oral HCV drugs with or without peg/rbv in combination, and then we will have 3 or more oral drugs in combination. Each drug company developing HCV oral drugs has at least 2 or more oral drugs in their develoment program so they are planning studies of 2 or more oral drugs in combination. Two companies, Vertex and BMS have already started such studies. BMS was the first in Jan 2010 to announce such a study where they are studying their HCV proease inhibitor and their potent NS5A inhibitor in combination both with and without peg/rbv in of note null-responders. This study was a major leap forward in that it was the first to advance into null-responders and the first of 2 oral rugs to begin. Since then in the past 2 months Abbott announced a study of their 2 oral drugs, and Boerhinger Ingelheim is planning such a study as well.

EASL 45th Annual Meeting
(European Association for the Study of the Liver)
April 14-18, 2010
Vienna, Austria

>From Ash To Cure - EASL April 14-18 2010


from Jules: I landed at Newark late yesterday afternoon Tuesday April 20 and was very glad to be home. But there were 7,000 attendees at the EASL conference in Vienna and many of our colleagues are still struggling to get home, although some have made it back yesterday as I did. People on their own & in groups traveled Monday or today to other cities anyway they could, by van, by car, by train, by plane, and although some got out Monday back to the USA many are in transit to other cities in Europe hoping to get out - to Munich, Rome, Lisbon, Madrid. Some people stuck in Europe are on medications of various types and struggling to deal with this. I have a better understanding now what it's like to serve overseas during wartime and then return home, because although I cannot compare what we went through in Europe at this time trying to get home what people are going through in Vienna and throughout Europe is quite difficult like veterans who saw devastation & death on the warfield. On the other hand the studies & data reported at EASL are all very encouraging and moving us all along to curing HCV. Here are links to reports posted as of this moment in time to the NATAP website but a number of reports I sent out by email with accompanying slides or poster tables etc imbedded in email reports have not yet been posted to the NATAP website. Of note there were 2 study data reports on genotype 2, so telaprevir and the Roche/pharmasset nucleoside RG7128 show good activity against genotype 2, although this is not as big a need as drugs for genotype 1 this is important also, although many don't realize this yet. Below are links to study reports with important developments in HCV protease inhibitors, a new target in NS5A with BMS reporting key early data on the potency of their NS5A inhibitor & with Presidio reporting for the first time in vitro data on their NS5A inhibitor program - very important to have this new class of drug, many companies have polymerase inhibitors with most companies having at least 2 classes of drugs they are developing. BMS has 3 classes - NS5A, protease & newly announced polymerase, so in my opinion this creates a new bar, all companies should have drugs in development in 3 different classes. Tibotec announced for the first time publicly and presented a poster announcing 2 new classes of HCV drugs now in addition to their protease, a nuke and a NNRTI. Roche reported very interesting & promising data in several oral & poster presentations from INFORM with 2 oral drugs with & without peg/rbv, a crucial oral presentation showing data from boosting their proteae with ritonavir which in early data looked good (look at that report), and of note a poster reporting data in patients starting 2 oral drugs and adding peg/rbv later showing a synergistic affect of using orals & interferon in prior nonresponders. Boerhinger Ingelheim reported new data in the SILENC study in an oral presentation late breaker on their HCV protease and it looks good, as well they reported in a poster 4 weeks data on their polymerase inhibitor in combination wit peg/rbv. Pharmasset reported very interesting data on the combination of 2 new nucleotide inhibitors, which are still their drugs. Merck of note reported the 1st data on their new HCV protease showing in vitro activity against 2 major HCV protease inhibitor mutations, 155 & 168, so this could be an important development. Vertex reported new data on their VX-222 polymerase inhibtor - 3 days monotherapy, showing it again to be potent. Abbott reported several posters on their program, but not major data, as they announced before the meeting earlier this year they have 3 oral drugs for which they are starting a study, a protease and 2 polymerase inhibitors, but this is not a study combining all 3, only 2. Gilead reported in a poster early data on their HCV protease inhibitor. Of note the Isreali researcher reported early new data finding vitamin D doubled SVR rates in patients in his study noting that this benefit may particularly accrue for people of dark color skin. Both boceprevir and telaprevir are now in phase 3 studies, the last step before getting FDA approval to sell them in the pharmacy so we will see new data from phase 3 I expect at AASLD in November. These 2 drugs will be the first step in the development and availability of multi-drug combinations with or without peg/rbv. For now & the near term future peg/rbv will be part of therapy & it remains to be seen in studies whether or how we can eliminate this therapy. I expect that with peg/rbv + orals therapy of 2-4 drugs we will be able to reduce duration of therapy for many patients down to 16, 12, or maybe 8 weeks. Of particular note HCV is NOT like HCV in many very important ways: HCV therapy is curative with 24 weeks; I expect that everyone in the USA can be cured if tested & if they receive good & proper care & treatment IF we have the proper programs in place upon launch of these drugs, and this is a big IF. HIV is different than HCV. HIV is lifetime therapy at least for now so we had many years to try to get it right. When the Ryan White Care Act came out initially in the mid-90s it took years before they realized they could treat drug users successfully. We do NOT have that amount of time in HCV. This is just one example of the differences between HIV & HCV, HCV is a very unique situation & if the drug companies & governments don't plan properly success is not guaranteed. If patients start getting drug resistance and it prevents successful therapy in large numbers of patients we will face very difficult barriers. There is no Ryan White Care Act-like program for HCV and it is unlikely there will be a large-sclae program or any Federal or State program for HCV to support the needed services & screening......more to come Jules Levin, NATAP