FDA will review two NS3/4A protease inhibitors, Merck’s boceprevir on April 27 and Vertex’s telaprevir on April 28. Both drugs have shown success in increasing hepatitis C cure rates when added to pegylated interferon and ribavirin. A couple of months back we asked our Hepatitis C Thought Leader panel to compare the two agents. Bottom-line: Our panel didn’t have a strong preference for either telaprevir over boceprevir, or vice-versa. Slight edge to telaprevir; with the overriding factor being shorter course of therapy for many patients. This will lower costs for other drugs; including interferon and EPO. There are obviously biases based on having worked more with one or the other, but they are both going to be viewed as roughly equivalent for efficacy (primary effect on viral load, and resistance development), safety and convenience.
“So I think the drugs are roughly comparable in terms of efficacy and side effects and duration of therapy. It would be difficult to say I would pick one over the other without these other extenuating circumstances like contracting and these kinds of deals. That is the part I haven’t been able to find any information on. I have talked about the data with lots of people. I have presented some of the data. I am familiar with the pros and cons of various studies from the presentations that were done and a variety of ad boards that we were at where these things were discussed. But what I haven’t found out is how either Merck or Vertex are going to price the product, what kind of deals they are going to have with managed care as they get close to launch”.
Ø There also wasn’t a sense that any next-generation protease inhibitor was going to be dramatically more effective than these first two. The “art” will be in their combination.
“It is going to be difficult because what is happening is we know these direct antivirals are very potent and, yes, there can be other targets on the protease side. These are the sort of NS3/4A ones and we know there are other site specific protease inhibitors which may be more potent in vitro. But I think overall they will pretty much have similar efficacy. It will be hard to sort of imagine there is one protease target which is better than something which targets something adjacent to the binding sites on the HCV genome. The most promising aspect is really the combination of protease inhibitors. That is where there may be a potential you can target, like an NS3/4A protease which something which is similar but binds at a different site. And I think that is where there may be some synergy in the future”.
Ø A complete review is available in that panel report. Ask and you’ll receive. For now we just want to note that Vertex has been much more active than Merck in pre-market conditioning efforts. Because telaprevir is going to be approved with a simpler regimen than boceprevir, we see Vertex et.al. expanding their target physician marketing to the Infectious Disease physicians; a group that is inexperienced in recognizing and treating liver complications. The three marketing messages that Vertex will share are:
o Shorter course of therapy with telaprevir than boceprevir (12-24-week vs. 48-week)
o Telaprevir is more potent than boceprevir
o Boceprevir’s lead-in strategy is too complex (notably, Vertex is now studying telaprevir in a lead-in protocol, so this last message is probably not going to be highlighted for too long)
“First of all, you can legitimately plan a shorter treatment regimen. Secondly, assuredly it is a more potent agent than boceprevir. And thirdly, I find the data easier to understand. Interesting comment. Let me do that third one first. Why do you say it that way? If you look at the boceprevir trials there is the lead-in and this that and the other thing and it seems to me that it is done on an ad-hoc basis rather than be planned ahead of time”.
“Some people just believe that Vertex is going to carry the day and they are going to have it all. I don’t know, maybe they will. They certainly have been out ahead with their marketing”.
“I do think that the folks at Vertex will have to make sure that their launch is very smooth. The success of their drug –and I think going into launch the slight edge right now goes to telaprevir compared to boceprevir – but how well they handle the rash I think will determine how well they are able to launch and gain marketshare. If they do a good job and their drug holds up good for them. They will do a very, very good job”.
“So you have probably heard more about telaprevir because they have been a little more aggressive in their promotional. They don’t call it that but, in fact, that is what it is. They are a little more aggressive in their promotional stuff because Vertex is a company with one product and it is telaprevir. So it has got to work for them”.
“In my opinion here slight edge to telaprevir – adding 12 weeks of telaprevir to peg interferon/ribavirin that is actually a pretty simple message isn’t it. I think that is easier than the lead in, even though in my opinion, I think the lead-in makes sense. If I am doing screening colons in the morning and seeing my few hepatitis C patients in the afternoon I am going to be more inclined to move over to using telaprevir just because I think it will take fewer resources. And so I think we will be extremely busy and the first wave will be non-responders”.